DEPARTMENT OF HEALTH AND HUMAN SERVICES 
 

CENTERS FOR DISEASE CONTROL AND PREVENTION
 

Advisory Committee on 

Immunization Practices (ACIP) 

Summary Report
 

June 24-25, 2015 

Atlanta, Georgia 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Table of Contents Pages 

Agenda 4-6 

Acronyms 7-8 

Wednesday: June 24, 2015 

Welcome and Introductions 9-21 

Meningococcal Vaccines 

 Introduction 

 GRADE: Evidence for use of MenB Vaccine in Adolescents and College Students 

 Considerations for Routine Use of MenB Vaccines in Adolescents 

 Public Comments 

 Proposed Recommendations / Vote 

 VFC Vote 

22-60 

General Recommendations on Immunization 

 Introduction 

 Various Topics 

 Proposed Recommendations / Vote 

60-70 

Novel Influenza Vaccines 

 Introduction 

 Influenza A (H5) Epidemiology Update 

71-76 

Influenza 

 Introduction 

 Influenza Vaccine Effectiveness Update 

 Quadrivalent Intradermal Influenza Vaccine 

 Influenza Vaccine Safety Update 

 High-Dose Influenza Vaccine Update 

 Proposed Recommendations / Vote 

76-98 

Smallpox Vaccine: Use in Laboratory Personnel 

 Introduction 

 Proposed Smallpox Vaccine Recommendations / Vote 

99-110 

Public Comments Day 1 110 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Thursday: June 25, 2015 

Agency Updates 

 Centers for Disease Control and Prevention (CDC) 

 Center for Medicare and Medicaid Services (CMS) 

 Department of Defense (DoD) 

 Department of Veteran’s Affairs (DVA) 

 Food and Drug Administration (FDA) 

 Heath Resources and Services Administration (HRSA) 

 Indian Health Services (I HS) 

 National Institutes of Health (NIH) 

 National Vaccine Advisory Committee (NVAC) 

 National Vaccine Program Office (NVPO) 

111-115 

Japanese Encephalitis Vaccine 

 Japanese Encephalitis Work Group Update 

116-117 

Pneumococcal Vaccines 

 Introduction 

 Intervals between PCV13 and PPSV23: Supporting Evidence and Rationale for Change 

 Proposed Recommendations / Vote 

117-133 

Combination Vaccines 

 Formation of Combination Vaccines Work Group 

133-134 

Human Papillomavirus (HPV) Vaccines 

 Introduction 

 9-valent HPV Vaccination for Persons Who Have Completed an HPV Vaccination Series 

 Cost-Effectiveness 

 Proposed Guidance 

134-151 

Pertussis 

 Introduction 

 Cocooning and Tdap Vaccination 

 Acellular Pertussis Vaccine Effectiveness among Children and Adolescents in the Setting of Pertactin-Deficient B. 

Pertussis, Vermont, 2011-2013 

151-165 

Herpes Zoster 

 Introduction 

 Update on Herpes Zoster Epidemiology and Vaccine Uptake 

 Results of GSK Phase 3 Study of Investigational Adjuvant-Based Zoster Vaccine 

165-174 

Public Comments Day 2 174 

Certification 175 

Membership Roster 176-185 

Meningococcal Letters 185-254 

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2:45 Influenza 

Introduction 

Influenza vaccine effectiveness update 

Quadrivalent intradermal influenza vaccine 

Influenza vaccine safety update 

Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) 

Centers for Disease Control and Prevention
 

1600 Clifton Road, NE, Tom Harkin Global Communications Center, Kent "Oz" Nelson Auditorium
 

Atlanta, Georgia 30333
 

June 24-25, 2015
 

AGENDA ITEM 

Wednesday, June 24th 

8:00 Welcome & 

Introductions 

PURPOSE 

8:30 Meningococcal Vaccines 

Introduction 

GRADE: evidence for use of MenB vaccine in 

adolescents and college students 

Considerations for routine use of MenB 

vaccines in adolescents 

Information 

& 

Discussion 

10:15 Public Comment - Meningococcal Vaccines 

10:45 Break 

11:00 Meningococcal Vaccines 

Proposed recommendations Vote 

VFC Vote VFC Vote 

11:30 General Recommendations on Immunization 

Introduction Information 

& 

Discussion 

Vote 

Various topics 

Proposed recommendations 

12:45 Lunch 

2:00 Novel Influenza Vaccines 

Introduction 

Influenza A (H5) epidemiology update 

Information 

& 

Discussion 

Information 

& 

Discussion 

PRESIDER/PRESENTER(s) 

Dr. Jonathan Temte (ACIP Chair) 

Dr. Cindy Weinbaum (Acting
 

Executive Secretary, ACIP;
 

CDC/NCEZID)
 

Dr. Lorry Rubin (ACIP, WG Chair)
 

Dr. Temi Folaranmi (CDC/NCIRD)
 

Ms. Jessica MacNeil 

(CDC/NCIRD)
 

Ms. Jessica MacNeil 

(CDC/NCIRD)
 

Dr. Jeanne Santoli (CDC/NCIRD)
 

Dr. Marietta Vàzquez (ACIP, WG 

Chair)
 

Dr. Ray Strikas (CDC/NCIRD)
 

Dr. Ray Strikas (CDC/NCIRD)
 

Dr. Doug Campos-Outcalt (ACIP,
 

WG Chair)
 

Dr. Sonja Olsen (CDC/NCIRD)
 

Dr. Ruth Karron (ACIP, WG Chair)
 

Dr. Brendan Flannery
 

(CDC/NCIRD)
 

Dr. Corey Robertson (Sanofi 

Pasteur)
 

Dr. Tom Shimabukuro
 

(CDC/NCEZID)
 

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 8:15 Japanese Encephalitis Vaccine 

Japanese Encephalitis Vaccines Work Group 

update 

 

 8:20 Pneumococcal Vaccines 

Introduction 

Intervals between PCV13 and PPSV23: 

supporting evidence and rationale for change 

Proposed recommendations 

Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

High dose influenza vaccine update 

Proposed recommendations 

Dr. Lisa Grohskopf (CDC/NCIRD) 

Vote Dr. Lisa Grohskopf (CDC/NCIRD) 

4:15 Break 

4:30 Smallpox Vaccine: Use in Laboratory Personnel 

Introduction 

Proposed smallpox vaccine recommendations 

Information 

& 

Discussion 

Vote 

Dr. Lee Harrison (ACIP, WG 

Chair) 

Dr. Brett Petersen (CDC/NCEZID) 

5:15 Public Comment 

5:30 Adjourn 

Thursday, June 25th 

8:00 Agency Updates 

CDC, CMS, DoD, DVA, FDA, HRSA, IHS, NVPO, 

NIH 

Information CDC and ex officio members 

Information Joseph Bocchini (ACIP, WG 

Chair) 

Information 

& 

Discussion 

Vote 

Dr. Nancy Bennett (ACIP, WG 

Chair) 

Dr. Miwako Kobayashi 

(CDC/NCIRD) 

Ms. Tamara Pilishvili 

(CDC/NCIRD) 

9:20 Break 

9:35 Combination Vaccines 

Formation of Combination Vaccines Work 

Group 

Information 

& 

Discussion 

Dr. Art Reingold (ACIP, WG 

Chair) 

9:45 Human Papillomavirus (HPV) Vaccines 

Introduction 

9-valent HPV vaccination for persons who have 

completed an HPV vaccination series 

Cost effectiveness 

Proposed guidance 

Dr. Joe Bocchini (ACIP, WG 

Chair) 

Dr. Lauri Markowitz 

(CDC/NCHHSTP) 

Dr. Harrell Chesson 

(CDC/NCHHSTP) 

Dr. Lauri Markowitz 

(CDC/NCHHSTP) 

Information 

& 

Discussion 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

11:00 Pertussis 

Introduction 

Cocooning and Tdap vaccination 

Acellular pertussis vaccine effectiveness among 

children and adolescents in the setting of 

pertactin-deficient B. pertussis, Vermont, 2011­

2013 

Information 

& 

Discussion 

Dr. Art Reingold (ACIP, WG 

Chair) 

Dr. Jennifer Liang (CDC/NCIRD) 

Dr. Lucy Breakwell (CDC/NCIRD) 

11:45 Herpes Zoster 

Introduction 

Update on herpes zoster epidemiology and 

vaccine uptake 

Results of GSK Phase 3 study of investigational 

adjuvant-based zoster vaccine 

Information 

& 

Discussion 

Dr. Ed Belongia (ACIP, WG Chair) 

Dr. Rafael Harpaz (ACIP/NCIRD) 

Dr. Thomas Heineman (GSK) 

12:45 Public 

Comment 

1:00 Adjourn 

Acronyms 

CDC Centers for Disease Control & 

Prevention NCHHSTP National Center for HIV, Hepatitis, STD 

andTB Prevention [of CDC/OID] 

CMS Centers for Medicare and Medicaid 

Services NCIRD CDC National Center for Immunization & 

Respiratory Diseases [of CDC/OID] 

DoD Department of Defense NCEZID National Center for Emerging and Zoonotic 

Diseases [of CDC/OID] 

DVA Department of Veterans Affairs NIH National Institutes of Health 

FDA Food and Drug Administration NVPO National Vaccine Program Office 

GRADE 

Grading of Recommendations 

Assessment, Development and 

Evaluation 

PCV13 13-valent Pneumococcal Conjugate Vaccine 

HPV Human Papillomavirus PPSV23 Pneumococcal Polysaccharide Vaccine 

HRSA Health Resources and Services 

Administration Tdap Tetanus, Diphtheria, and acellular Pertussis 

Vaccine 

IHS Indian Health Service VFC Vaccines for Children 

MenB Meningococcal B 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Acronyms 

AAFP American Academy of Family Physicians 

AAP American Academy of Pediatrics 

ABCs Active Bacterial Core Surveillance 

ACA Affordable Care Act 

ACHA American College Health Association 

ACIP Advisory Committee on Immunization Practices 

ACNM American College of Nurse Midwives 

AE Adverse Events 

AFP American Family Physicians 

aHCST Autologous Hematopoietic Stem Cell Transplant 

AHIP America’s Health Insurance Plans 

AMA American Medical Association 

ANA American Nurses Association 

ASTHO Association of State and Territorial Health Officials 

BMI Body Mass Index 

BIO Biotechnology Industry Organization 

BMBL Biosafety in Microbiological and Biomedical Laboratories 

CDC Centers for Disease Control and Prevention 

CEJA Council on Judicial and Ethic Affairs, AMA 

ChAd3-EBO Z Chimpanzee Adenovirus 3-Based Vaccine 

CICP Countermeasures Injury Compensation Program 

CIN Cervical Intraepithelial Neoplasia 

CISA Project Clinical Immunization Safety Assessment Project 

CMS Center for Medicare and Medicaid 

COI Conflict of Interest 

COID Committee on Infectious Disease, AAP 

CSAPH Council on Science and Public Health, AMA 

CSTE Council of State and Territorial Epidemiologists 

DMID NIAID Division of Microbiology and Infectious Diseases 

DoD Department of Defense 

DRC Democratic Republic of the Congo 

DSMB Data Safety Monitoring Board 

DVA Department of Veterans Affairs 

EBR Evidence-Based Recommendations 

EEOC Equal Employment Opportunity Commission 

EGAPP Evaluation of Genomic Applications in Practice and Prevention 

EIP Emerging Infections Program 

ELISA Enzyme-Linked Immunosorbent Assay 

FDA Food and Drug Administration 

FLU VE Influenza Vaccine Effectiveness Network 

GBS Guillain-Barré Syndrome 

gE Glycoprotein E 

GMT Geometric Mean Titer 

GRADE Grading of Recommendation Assessment, Development and Evaluation 

GSK GlaxoSmithKline 

HD-IIV High-Dose Inactivated Influenza Vaccine 

HI Hemagglutination Inhibition 

HPV Human Papillomavirus 

HRSA Health Resources and Services Administration 

hSBA Serum Bactericidal Activity using Human Complement 

HZ Herpes Zoster 

HZAC HZ Adjudication Committee 

HZO Herpes Zoster Ophthalmicus 

HZ/su Herpes Zoster Adjuvanted Subunit Vaccine 

ICD International Classification of Diseases 

IDSA Infectious Disease Society of America 

IHS Indian Health Service 

IIS Immunization Information System 

IIV Inactivated Influenza Vaccine 

ILI Influenza-Like Illness 

ILINet Influenza-Like Illness Surveillance Network 

IND Investigational New Drug 

IPD Invasive Pneumococcal Disease 

IPV Inactivated Poliomyelitis Vaccine 

ISO Immunization Safety Office 

IT Information Technology 

JE Japanese Encephalitis 

LAIV Live Attenuated Influenza Vaccine 

LCI Laboratory-Confirmed Influenza 

LMP Last Menstrual Period 

LSU Louisiana State University 

MAARI Medically Attended Acute Respiratory Illness 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

MATS Meningococcal Antigen Typing System 

MedDRA Medical Dictionary for Regulatory Activities 

MCV4 Meningococcal Conjugate Vaccine 

MenACWY Quadrivalent Meningococcal Conjugate Vaccine 

MenB Serogroup B Meningococcal Disease 

MMR Measles, Mumps, Rubella 

MMWR Morbidity and Mortality Weekly Report 

MPL Monophsophoryl Lipid 

MSM Men Who Have Sex With Men 

mTVC Modified Total Vaccinated Cohort 

NACI National Advisory Committee on Immunization, Canada 

NEJM New England Journal of Medicine 

NIAID National Institute of Allergy and Infectious Diseases 

NAIP National Adult Immunization Plan 

NIP National Immunization Program 

NNDSS National Notifiable Disease Surveillance System 

NNV Number Needed to Vaccinate 

NCHHSTP National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 

NCIRD National Center for Immunization and Respiratory Diseases (of CDC/CCID) 

NMA National Meningitis Association 

NNV Number Needed to Vaccinate 

NVAC National Vaccine Advisory Committee 

NVPO National Vaccine Program Office 

OAH Office of Adolescent Health 

OPM Office of Personnel Management 

OWM Office of Women’s Health 

PCR Polymerase Chain Reaction 

PCV Pneumococcal Conjugate Vaccine 

PHN Post-Herpetic Neuralgia 

PIDS Pediatric Infectious Diseases Society 

pIMD Potential Immune Mediated Disease 

PMI Precision Medicine Initiative 

PRAMS Pregnancy Risk Assessment Monitoring System 

PREP Act Public Readiness and Emergency Preparedness Act 

PREVAIL Partnership for Research on Ebola Vaccines in Liberia 

PPSV Pneumococcal Polysaccharide Vaccine 

QALYs Quality Adjusted Life Years 

QIV-ID Fluzone Intradermal® Quadrivalent Vaccine 

QoL Quality of Life 

qPCR Quantitative PCR 

RA Rheumatoid Arthritis 

RCA Rapid Cycle Analysis 

RCT Randomized Controlled Trial 

RNA Ribonucleic Acid 

RT-PCR Reverse Transcription Polymerase Chain Reaction 

SAB Spontaneous abortion 

SAEs Serious Adverse Events 

SD-IIV Standard-Dose Inactivated Influenza Vaccine 

SHEA Society for Healthcare Epidemiology of America 

SIVAC Supporting National Independent Immunization and Vaccine Advisory Committees 

SPS Shingles Prevention Study 

Tdap Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis 

TIV-HD Trivalent, Inactivated Influenza Vaccine 

UK United Kingdom 

US United States 

USAMRIID US Army Medical Research Institute of Infectious Disease 

USPHP United States Public Health Service 

USPSTF US Preventive Services Task Force 

VAERS Vaccine Adverse Event Reporting System 

VE Vaccine Effectiveness 

VSVdeltaG-ZEBOV Vesicular Stomatitis Virus-Based Vaccine 

VFC Vaccines for Children 

VHA Veterans Health Administration 

VICP Vaccine Injury Compensation Program 

VSD Vaccine Safety Datalink 

WG Work Group 

WHO World Health Organization 

WIR Wisconsin Immunization Registry 

YF Yellow Fever 

VLP Virus-Like Particle 

VZV Varicella Zoster Virus 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Welcome, Introductions, & Farewells 

Welcome 

Jonathan Temte, MD, PhD 

ACIP Chair 

Dr. Cindy Weinbaum 

Acting Executive Secretary, ACIP / CDC 

Following Dr. Temte’s greeting and call to order, Dr. Weinbaum welcomed everyone to the June 

2015 Advisory Committee on Immunization Practices (ACIP) meeting. She indicated that the 

proceedings of this meeting would be available to people not in attendance via the World Wide 

Web, and welcomed those who could not attend the meeting in person. She then recognized 

several others in the room who were to be present throughout the duration of the meeting to 

assist with various meeting functions: Stephanie Thomas, Natalie Greene, Jean Smith, and 

Chris Caraway. 

Dr. Weinbaum noted that handouts of the presentations were distributed to the ACIP members 

and were made available for others on the tables outside of the auditorium. Slides presented 

during this meeting will be posted on the ACIP website approximately two weeks after the 

meeting concludes, the live webcast will be posted within four weeks following the meeting, and 

the meeting minutes will be available on the website within approximately 90 days following this 

meeting. Members of the press interested in conducting interviews with ACIP members were 

instructed to contact Ian Branam for assistance in arranging interviews. 

The next ACIP meeting will convene at CDC on Wednesday and Thursday, October 21-22, 

2015. Registration for all meeting attendees is required and will be open Friday, June 26, 2015, 

on the ACIP website. The registration deadline for Non-US citizens is September 30, 2015 and 

for US citizens registration closes October 7, 2015. Registration is not required for webcast 

viewing. As a reminder for non-US citizens attending ACIP meetings, completion of several 

forms is required for each meeting at the time of registration. It is important that these forms 

are submitted within the required time frame. Stephanie Thomas, the ACIP Committee 

Management Specialist, will be able to help with any questions about the process. 

Dr. Weinbaum recognized and welcomed the following visitors: 

 Dr. Audry Mulumba, Medical Director, Expanded Program of Immunization (EPI), 

Democratic Republic of the Congo (DRC) 

 Ms. Yolande Masembe, Epidemiologist, World Health Organization (WHO), DRC 

 Dr. Antoinette Ba-Nguz, Africa Coordinator, Supporting National Independent Immunization 

and Vaccine Advisory Committees (SIVAC), a Bill and Melinda Gates Foundation funded 

initiative to strengthen national technical advisory committees for immunization 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

In addition, Dr. Weinbaum recognized and welcomed the following Liaison Representatives: 

 Dr. Leonard Friedland, GlaxoSmithKline (GSK), Representing the Biotechnology Industry 

Organization (BIO) on Day 1 

 Dr. Eddy Bresnitz, Merck, Representing BIO on Day 2 

 Ms. Carol Hayes, Representing both the American College of Nurse Midwives (ACNM) and 

the American Nurses Association (ANA) 

Dr. Weinbaum indicated that topics presented during ACIP meetings include open discussion 

with time reserved for public comment. She explained that time for public comment pertaining 

to topics on the agenda was scheduled following the afternoon sessions each day, and that 

time for public comments also may be provided prior to specific votes by ACIP to enable these 

comments to be considered before the vote. During this meeting, there were three public 

comment opportunities: 10:15 and 5:15 on Day 1 and at 12:45 PM on Day 2. People who 

planned to make public comments were instructed to visit the registration table at the rear of the 

auditorium where Ms. Stephanie Thomas would record their name and provide information on 

the process. People making public comments were instructed to provide 3 pieces of 

information: Name, Organization if applicable, and any conflicts of interest (COI). Registration 

for public comment was solicited in advance of this meeting through the Federal Register. 

Given time constraints, each comment was limited to 3 minutes. Participants unable to present 

comments during this meeting were invited to submit their comments in writing for inclusion in 

the meeting minutes. 

Regarding recommendations, ACIP uses a standard process to systematically collect and 

evaluate evidence behind each recommendation. More information about the Grading of 

Recommendation Assessment, Development and Evaluation (GRADE) process can be found 

on the ACIP website. Key factors for developing recommendations include the balance of 

benefits and harms, type or quality of evidence, values and preferences, and health economic 

analyses. The ACIP recommendation categories are: 

 Category A: A recommendation that applies to all persons in an age- or risk-based group. 

 Category B: A recommendation for individual clinical decision making. 

 No recommendation for an unresolved issue. 

Vaccine safety issues will continue to be presented at every ACIP meeting. During this 

meeting, these issues were included as part of specific topic presentations. 

Regarding ACIP implications of the Affordable Care Act (ACA), ACIP recommendations 

become policy following approval by the CDC Director and publication in the Morbidity and 

Mortality Weekly Report (MMWR). The ACA was enacted in 2010, and requires insurance 

coverage for recommended immunizations without copays/deductibles when provided by an innetwork provider. Health plans have one plan year from MMWR publication to implement 

recommendations according to CDC immunization schedules, including recommendations 

illustrated in the graphics and those described in footnotes. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

During every meeting, an update is provided on the status of ACIP recommendations. There 

have been three ACIP publications since February 2015, which are reflected in the following 

table: 

Recommendations and immunization schedules can be downloaded from the ACIP website. 

ACIP has a policy that every three to five years each recommendation is reviewed, and then 

renewed, revised, or retired. 

Applications for ACIP membership are due no later than November 13, 2015 for the 4-year term 

beginning July 2016. Detailed instructions for submission of names of potential candidates to 

serve as ACIP members may be found on the ACIP web site: 

E-mail: acip@cdc.gov Web homepage: http://www.cdc.gov/vaccines/acip/index.html 

Nominations: http://www.cdc.gov/vaccines/acip/committee/req-nominate.html 

A current CV, at least one recommendation letter from a non-federal government employee, 

and complete contact information are required. These may be submitted as e-mail attachments 

to Dr. Jean Clare Smith at jsmith2@cdc.gov 

To summarize COI provisions applicable to the ACIP, as noted in the ACIP Policies and 

Procedures manual, members of the ACIP agree to forgo participation in certain activities 

related to vaccines during their tenure on the committee. For certain other interests that 

potentially enhance a member’s expertise while serving on the committee, CDC has issued 

limited COI waivers. Members who conduct vaccine clinical trials or serve on data safety 

monitoring boards (DSMBs) may present to the committee on matters related to those vaccines, 

but these members are prohibited from participating in committee votes on issues related to 

those vaccines. Regarding other vaccines of the concerned company, a member may 

participate in discussions, with the proviso that he/she abstains on all votes related to the 

vaccines of that company. It is important to note that at the beginning of each meeting, ACIP 

members state any COIs. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Before officially beginning the meeting, Dr. Temte called the roll to determine whether any ACIP 

members had conflicts of interest. The following conflicts of interest were declared: 

 Dr. Belongia: Receives research funding from Medimmune and has a conflict for influenza. 

 The remainder of the ACIP members declared no conflicts. 

Farewell to Parting ACIP Members 

Jonathan Temte, MD, PhD 

ACIP Chair 

Dr. Temte shared some final comments, as his term as ACIP Chair would come to a close at 

the end of this meeting. He also recognized the other ACIP members who reached the end of 

their four-year terms and were rotating off of the committee, and presented each of them with a 

Certificate of Appreciation and a letter from Dr. Frieden, CDC’s Director. 

First, he showed the following seating chart and photograph, pointing out that for a number of 

years he and Drs. Bocchini and Campos-Outcalt sat together and that he was able to find a 

photograph from those days: 

With Drs. Bocchini and Campos-Outcalt rotating off of the committee, Dr. Temte observed that 

ACIP was losing about 20 years’ worth of experience. 

Joseph A. Bocchini, Jr. MD 

Dr. Bocchini continues to practice Pediatric Infectious Disease at Louisiana State University 

(LSU) in Shreveport. He has a significant number of research interests, including special 

interest in vaccines; neonatal sepsis; and pharmacokinetics, toxicities, and interactions of 

antimicrobial agents in children. He has served as the Chair of the Human Papillomavirus 

(HPV) Work Group (WG) and the Yellow Fever/Japanese Encephalitis (YF/JE) WG. He served 

as the ACIP Liaison for American Academy of Pediatrics (AAP) Committee on Infectious 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Diseases (COID). Two of his publications include Immunizing adolescents: a selected review of 

recent literature and US recommendations (2015) and Improving vaccine risk/benefit 

communication with an immunization education package: a pilot study (2002). Dr. Temte 

expressed appreciation for Dr. Bocchini’s wisdom, knowledge, and enthusiasm throughout the 

last 11 years. 

Doug Campos-Outcalt MD, MPA 

Dr. Campos-Outcalt is currently a Senior Lecturer at the University of Arizona College of 

Medicine in Phoenix. He has considerable public health experience, including serving as a 

consultant to Papua New Guinea for two years. He also brings a lot of evidence-based science 

to the committee. He has served as the American Academy of Family Physicians (AAFP) 

liaison to the United States Preventive Services Task Force (USPSTF), as well as a member of 

the evidence-based Evaluation of Genomic Applications in Practice and Prevention (EGAPP) 

Working Group (EWG). He has served as the ACIP Chair for the H5N1 WG, and has been 

involved with the Meningococcal, Hepatitis, Evidence-Based Recommendations (EBR), and 

General Recommendations WGs. Some of his publications have included Female-to-female 

transmission of syphilis: a case report (2002), Pedestrian fatalities by race/ethnicity in Arizona, 

1990-1996 (2002), and Catching up on the latest USPSTF recommendations (2015). Though 

he is greatly appreciated and will be missed as a member, Dr. Campos-Outcalt plans to 

continue to help with GRADE support. 

Marietta Vazquez, MD 

Dr. Vazquez is Associate Professor of Pediatrics and Nursing at Yale School of Medicine in 

New Haven, Connecticut. Her research interests are in evaluating the effectiveness of pediatric 

vaccines, long-term outcomes of children infected with Lyme disease, and clinical epidemiology 

of newly diagnosed-respiratory infections in children. She has served as Chair of ACIP’s 

General Recommendations and Rotavirus WGs, and as a member of the Meningococcal and 

Pertussis WGs. Some of her publications included Effectiveness of varicella vaccine in children 

infected with HIV (2010) and Conservation of the Respiratory Syncytial Virus SH gene (2000). 

Dr. Temte thanked Dr. Vazquez for her enthusiasm and wisdom on the committee. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dan Hopfensperger 

Dr. Temte also expressed gratitude to Dan Hopfensperger who retired on June 10, 2015 from 

his position as Wisconsin Immunization Program Director, Wisconsin Division of Health 

Services. He was the longest serving state immunization program manager at 38 years. He 

was instrumental in the development and maturation of the Wisconsin Immunization Registry 

(WIR). 

Dr. Temte expressed gratitude to Dr. Jean Smith who he deemed the “grease and glue” in that 

she has been instrumental in lubricating the system, making it work, and holding it together 

behind the scenes. He shared the following email from Dr. Smith: 

He quipped that Dr. Smith always tries to make sure that ACIP does the right thing, and shared 

the following diagram that she created for the members to address the ongoing clockwise/ 

counterclockwise issue: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Temte shared the following quote to illustrate what he learned from ACIP: 

“Poor fool[s], with all this sweated lore,
 

[We] stand no wiser than we were before.
 

Master and Doctor are our titles;
 

For [51] years now, without repose,
 

[We've] held [our] erudite recitals
 

And [coaxed recommendations] by the nose.
 

And round [we] go,
 

on crooked ways or straight,
 

And well [we] know that
 

ignorance is our fate,
 

And this [we] hate.”
 

Faust 

Johann Wolfgang von Goethe, 1806 

He pointed out that ACIP members find that no matter how much information they have, it is 

never enough. In 2010, ACIP adopted GRADE. At the time, he heard rumbling that GRADE 

would turn people into numbers. He played a clip from 42 years ago from Jacob Bronowski 

who was a Polish Mathematician. Dr. Temte said that he was going to play this clip during his 

first ACIP meeting as Chair, but Dr. Pickering would not let him. He quipped that this was to get 

back at Dr. Pickering in his absence: 

“It’s said that science will dehumanize people and turn them into numbers. That’s false, 

tragically false. Look for yourself. This is the concentration camp and crematorium at 

Auschwitz. This is where people were turned into numbers. Into this pond were flushed 

the ashes of some four million people. And that was not done by gas. It was done by 

arrogance. It was done by dogma. It was done by ignorance. When people believe 

that they have absolute knowledge, with no test in reality, this is how they behave. This 

is what men do when they aspire to the knowledge of gods. 

Science is a very human form of knowledge. We are always at the brink of the known. 

We always feel forward for what is to be hoped. Every judgment in science stands on 

the edge of error and is personal. Science is a tribute to what we can know although we 

are fallible . . . 

We have to cure ourselves of the itch for absolute knowledge and power... 

We have to touch people.” 

Knowledge or Certainty
 

The Ascent of Man, BBC
 

Jacob Bronowski, 1973
 

Interestingly, Jacob Bronowski was the Director of the Salk Institute. ACIP deals with a lot of 

information, but also must put it into the context of the human element. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Temete shared the following lyrics from a Coldplay song and lines from a T.S. Eliot poem: 

“I was just guessing at numbers and figures
 

Pulling your puzzles apart
 

Questions of science, science and progress
 

Do not speak as loud as my heart”
 

The Scientist 

A Rush of Blood to the Head 

Coldplay, 2002 

“Where is the Life 

we have lost in living?
 

Where is the wisdom
 

we have lost in knowledge?
 

Where is the knowledge 

we have lost in information?”
 

T. S. Eliot 

The Rock, 1934 

In an effort to put this all together, Dr. Temte quoted the following from the Grinch in Dr. Seuss’s 

“How the Grinch Stole Christmas” from 1957 with a little embellishment: 

“[They] puzzled and puzzled till [their] puzzler was sore.
 

Then [ACIP] thought of something [they] hadn’t before.
 

Maybe [recommendations], [they] thought...
 

don’t come from a score.
 

Maybe recommendations, perhaps...
 

[mean] a little bit more!”
 

The Grinch 

How the Grinch Stole Christmas 

Dr. Seuss. Random House; 

November 24, 1957 

With the GRADE process, ACIP gathers information. But after the information is collected, it is 

filtered through topics such as cost-effectiveness, balances of harms and benefits, and values 

and preferences. Dr. Temte shared the following excerpt from a public comment: 

“We worry about cost-effectiveness.
 

Is this cost-effective?
 

Is Ethan cost-effective?...
 

I say to you one baby, one child,
 

one teen is too many,
 

especially when it comes to being yours.”
 

Frankie Milley 

Founder/National Director, Meningitis Angels 

Public Comment, ACIP October 23/24, 2013 

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This reminded Dr. Temte of a conversation with Dr. Mike Marcy who said, “When it comes to 

hard recommendations, what would you do for your child?” He then shared the following Calvin 

and Hobbes to illustrate the problem with science: 

Dr. Temte pointed out that during this meeting’s meningococcal session, there would be an 

unprecedented number of public comments. As of last count, approximately 40 letters had 

been received on this topic. This included a letter with approximately 1200 co-signatures and a 

petition with 601 co-signatures. He pointed out that this reflected ACIP’s position as a federal 

advisory committee. Through the GRADE process, it is ACIP’s duty not only to review all of the 

evidence, but also to consider other issues such as values and preferences. With that in mind, 

Dr. Temte emphasized that public comments must be taken into consideration. 

As a child, Dr. Temte said he first heard about “continual and fearless sifting and winnowing” 

from his father, who was a University of Wisconsin Professor as well. He emphasized that for 

ACIP, it is important to encourage “continual and fearless sifting and winnowing by which alone 

the truth can be found”: 

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In closing, Dr. Temte reminded everyone that the inscription on the ACIP bell reads, “May The 

ACIP Recommendations Always Ring Clearly.” The bell was gifted to ACIP by Dr. Samuel Katz 

in 1993: 

Farewell to Dr. Temte 

Anne Schuchat, MD 

Cindy Weinbaum, MD 

Jean Clare Smith, MD, MPH 

Dr. Schuchat thanked Dr. Temte for his incredible service, as well as the incredible material of 

his life that she featured in her farewell slideshow. Dr. Temte began his education in Iowa 

studying zoology and went on to earn an MD and PhD, featuring families throughout his career. 

The subject of Dr. Temte’s PhD dissertation was harbor seals and fertile periodicity: 

Betty and pup Lucille 

Madison Wisconsin 1983 

Subject of Dr. Temte’s PhD Dissertation 

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Dr. Temte and recovering abandoned harbor 

seal pup, Oregon coast 

The idea of the circle of life became a theme in Dr. Temte’s career. He continued in family 

medicine in Wisconsin, and continued to carry out the full spectrum of family medicine until he 

dropped obstetrics in 2000 when his own family made him realize that delivering other people’s 

babies was a little “too scary.” 

Dr. Temte’s attraction to vaccines dates back to the first Rubella Elimination meeting he 

attended at CDC on October 29, 2004. He has continued that interest in the international 

arena. In 2013, Dr. Li Li, the Director of the National Immunization Program in China, spent an 

exchange with CDC in Atlanta and also visited Dr. Temte to learn about implementation and 

use of the Wisconsin Immunization Registry. Dr. Li Li invited Dr. Temte to China where he 

presented a GRADE seminar to China’s ACIP equivalent. A favorite memory was a special 

“five-face” meal Dr. Temte enjoyed while there. 

Dr. Temte’s last three publications literally “span the waterfront” from the Pacific harbor seal, 

Betty, the oldest seal on record to give birth at 42, to his entry into the climate change debates 

and his passion for vaccine acceptance and misconceptions: 

 Temte JL, Flynn E. Phenomenal advanced age of pupping in a captive Pacificharbor seal 

(Phoca vitulina richardsi). Zoo Biology. 2015 [accepted]. 

 Barrett B, Charles JW, Temte JL. Climate change, human health, and epidemiological 

transition. Prev Med. 2015;70:69-75. 

 Epling JW, Savoy ML, Temte JL, Schoof BK, Campos-Outcalt D. When vaccine 

misconceptions jeopardize public health. J Fam Pract. 2014;63(12):E1-7. 

Many people leave ACIP and experience a post-partum depression of sorts. However, Dr. 

Temte’s fishing buddies have offered to help him ease the pain and with the great family that he 

enjoys, it is unlikely that Dr. Temte will suffer post-partum depression as he leaves ACIP. While 

ACIP is busy with the October 2015 meeting, he will be training for his next 5K. 

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In closing, Dr. Schuchat shared the following poem from the CDC/ACIP family in appreciation 

for Dr. Temte’s service as ACIP Chair: 

Farewell to Dr. Temte
 

Whose tank is never empty
 

As Chair he’s now quite comfy
 

No risk of Humpty Dumpty
 

In case you missed the memo
 

Let me provide a demo
 

Pronunciation T-E-M-T-E
 

No relative of K-E-M-P-E see
 

He kept the schedules calm
 

‘Til pneumo dropped a bomb
 

We’ll need an extra meeting
 

The conference lines were bleeping
 

His temperament so staid
 

He’s passionate for GRADE
 

His welcomes always warm
 

They’ll melt a Southern storm
 

Of course, we’re going to miss him
 

So go ahead and kiss him
 

Unless that is a no, no
 

We better check with MASO
 

Dr. Schuchat concluded that personally, it had been wonderful working with Dr. Temte. For 

those attending an ACIP meeting for the first time, she explained that this is not how meetings 

usually begin. However, Dr. Temte put his own personal touch on ACIP’s deliberative values 

and the GRADE process. 

Dr. Weinbaum presented Dr. Temte with a note from Dr. Larry Pickering in appreciation of their 

long work together, a letter from Dr. Frieden, and a Certificate of Appreciation. 

Dr. Smith indicated that when she was in internal medicine practice in Boston for 10 years 

before coming to the CDC, she went to an antiquarian book fare one day where she found a 

certificate dated 1792: 

“To Dr. Welch: Please to inoculate two children of McGower on account of the town of 

Boston agreeable to the vote for that purpose.” 

W. Smith 

Overseer of the Poor 

This was an instruction to Dr. Welch in Boston, Massachusetts, Overseer of the Poor, to 

administer smallpox variolation to two children in August 1792. Dr. Smith noted that the 

certification was in immaculate condition and cost her $1.00. She also indicated that Dr. Jose 

Romero provided a chapter called “Early Efforts of Controlled Variolation Vaccination and 

Isolation and Quarantine” from a book titled “Smallpox and Its Eradication.” 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Smith noted that in the 1980s, the predecessor of the National Immunization Program (NIP) 

created several Dr. Seuss posters and adapted language from his children’s books to contain 

immunization messages. She presented Dr. Temte with a framed poster with language from “If 

I Ran the Zoo.” 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Introduction 

Lorry Rubin, MD 

Chair, Meningococcal Work Group

Advisory Committee on Immunization Practices 

Dr. Rubin reminded everyone that two serogroup B Meningococcal (MenB) vaccines are 

licensed in the United States (US) and approved for use in persons 10 through 25 years of age: 

 MenB-FHbp (Trumenba®

, Pfizer) licensed on October 29, 2014 

 MenB-4C (Bexsero®, Novartis) licensed on January 23, 2015 

Both vaccines were licensed under an accelerated pathway. MenB vaccines are distinct from 

MenACWY conjugate vaccines because protection is based upon developing immunity to 

bacterial proteins rather than to capsular polysaccharides. Recent presentations to ACIP 

regarding MenB vaccines have included the following: 

 February and June 2014 

 Epidemiology of meningococcal disease outbreaks and outbreaks of serogroup B 

meningococcal disease on university campuses 

 Interim guidance for the use of a MenB vaccine under a CDC-sponsored expanded 

access investigational new drug (IND) 

 October 2014 

 Safety and immunogenicity for MenB-FHbp and MenB-4C 

 Epidemiology of serogroup B meningococcal disease in the US 

 Considerations for use of MenB vaccines in the US 

 February 2015 

 Considerations for use of MenB vaccines in persons at increased risk, with 

discussion and a vote 

The ACIP recommendation for use of MenB vaccine in persons at increased risk for 

meningococcal disease, which is a Category A recommendation, is as follows: 

A serogroup B meningococcal (MenB) vaccine series should be administered to persons 

aged ≥10 years at increased risk for meningococcal disease. (Category A) This 

includes: 

 Persons with persistent complement component deficiencies1 

 Persons with anatomic or functional asplenia2 

 Microbiologists routinely exposed to isolates of Neisseria meningitidis 

 Persons identified to be at increased risk because of a serogroup B 

meningococcal disease outbreak 

1

Including inherited or chronic deficiencies in C3, C5-9, properdin, factor D, factor H, or taking eculizumab (Soliris®) 2

Including sickle cell disease 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The activities since the last ACIP meeting resulted in a Policy Note regarding the use of MenB 

vaccines in persons aged ≥10 years at increased risk for serogroup B meningococcal disease 

that was published on June 12, 2015. The WG has been reviewing the available safety, 

immunogenicity, and epidemiological data and discussing policy options for broader use of 

MenB vaccines in adolescents and college students. Policy options for broader use of MenB 

vaccines concern administration of a MenB vaccine series at 11 to 12 years of age with an 

anticipated booster at 16 years of age. Also under consideration is administration of the 

vaccine at 16 years of age, 18 years of age, or among college students only. The 

recommendation options are: 

 Category A (for all persons in an age- or risk-factor-based group) 

 Category B (for individual clinical decision making) 

 No recommendation 

Presentations during this session include the following: 

 GRADE: Evidence for use of MenB vaccines in adolescents and college students 

 Considerations for routine use of MenB vaccines in adolescents 

 Public comment 

 Proposed policy option language and vote 

 VFC vote 

MenB vaccines certainly are challenging for ACIP. Of course, the goal is to prevent the largest 

proportion of cases of meningococcal disease possible. The recently licensed MenB vaccines 

are an important step forward. However, data for making policy decisions for vaccine use are 

not complete in terms of effectiveness, strain coverage in the US, duration of protection, effect 

on carriage and herd immunity, and expanded safety. In addition, the burden of serogroup B 

meningococcal disease in adolescents and young adults is currently low. 

GRADE: Evidence for Use of MenB Vaccine in Adolescents and College Students 

Temitope A. Folaranmi MD, MPH, MPP

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention 

Dr. Folaranmi presented the GRADE evaluation for use of MenB vaccines in adolescents and 

young adults, including college students. He reviewed the study questions for GRADE, the 

modified assessment for the quality of disease burden, the breadth of MenB strain coverage, 

and the GRADE assessment for evidence of outcomes. The study question addressed was: 

“Should MenB vaccines be routinely administered to all adolescents and young adults 

(including college students)?” 

There are two MenB vaccines licensed in the US. MenB-4C (Bexsero®) is a multi-component 

vaccine manufactured by Novartis, now GSK, and is a two-dose series. MenB-FHbp 

(Trumenba®) is a bivalent recombinant lipoprotein vaccine manufactured by Pfizer and is a 

three-dose series. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

After selecting the study question, the next step in the GRADE process was to select outcomes 

that the WG believed to be important and critical to answer this question. This table shows 

outcomes that were ranked critical for the study questions. The first two outcomes were rated 

using a modified assessment since they are surveillance data, and the last five outcomes were 

assessed using GRADE: 

Regarding the quality of meningococcal disease burden data, since the incidence of 

meningococcal disease has reached historic lows in the US in recent years, the WG felt that 

rating the quality of disease burden data would be a key component for this assessment. 

However, because these data were from surveillance and no intervention was tested, the WG 

could not evaluate the data in the GRADE format. Instead, they assessed the disease burden 

data for accuracy, applicability, and representativeness. The US meningococcal incidence data 

come from two sources: the Active Bacterial Core surveillance (ABCs) and the National 

Notifiable Disease Surveillance System (NNDSS). ABCs is an active surveillance system of 10 

US sites that is used to estimate incidence of meningococcal disease in the US. It is limited to 

only culture-confirmed cases, and therefore, an 18% correction factor is added to account for 

polymerase chain reaction (PCR)-confirmed cases. ABCs provides data on a variety of factors, 

including historical trend, risk factors, vaccination, and molecular data. 

However, due to the low case counts in ABCs in recent years, an integrated approach for 

meningococcal disease surveillance data is being used. This approach includes NNDSS, a 

passive surveillance system that captures information on all cases, including cases confirmed 

by PCR only and those with clinically compatible illness. Historically, serogroup and caseoutcome information has been limited, so these have been supplemented by ABCs and health 

departments since 2005. A capture-recapture analysis that was performed in Maine from 2001 

to 2006 demonstrated high sensitivity of state surveillance data when compared to hospital 

discharge records. Accuracy of disease burden data was improved when using an integrated 

approach to surveillance. Both ABCs and NNDSS surveillance systems were determined to be 

applicable, as they both capture meningococcal disease incidence in adolescents and young 

adults. Although ABCs is limited to 10 sites and may not be representative of the national 

meningococcal disease incidence, NNDSS is reported by all states and is considered 

representative of national meningococcal disease incidence. 

To complete the assessment of the burden of disease data quality, the WG reviewed morbidity 

and mortality data, using mortality data collected from ABCs and NNDSS, and long-term 

sequelae data that were captured in published manuscripts. Estimates of case-fatality rates 

and long-term sequelae varied depending upon the source, and ranged from 2% to 10% for 

case-fatality rate and 5% to 50%1 for long-term sequelae. ABCs and NNDSS capture all 

meningococcal data among adolescents. However, serogroup-specific information may not 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

always be available. Published reports of long-term sequelae from all-cause bacterial 

meningitis are often hospital-based studies with small sample sizes, and have limited 

information on age and serogroups. Based on the evaluation of meningococcal disease 

incidence, mortality, and morbidity data, minor limitations were found in terms of 

representativeness, accuracy, and applicability. However, the WG did not feel that this 

significantly affected the quality of its burden of disease estimates [

1

Bedford et al., BMJ 2001, 

323: 533-7;Chandran et al., PIDJ 2011, 30:3-6.; Erickson and De Wals. CID 1998, 26:1159-64; 

Kaplan et al., Pediatrics 2006, 118(4):e979-84]. 

In terms of the modified assessment of strain coverage, vaccine targets for MenB vaccines are 

antigenically diverse and are variably expressed among circulating MenB strains in the US. 

However, there are no data demonstrating bactericidal activity against all circulating invasive 

MenB strains in the US. For the Pfizer vaccine, MenB-FHbp, FHbp sequence analysis and 

surface expression by flow cytometry was performed for an epidemiologically representative 

collection of 1263 MenB strains, of which 432 were US isolates. FHbp was expressed in about 

95% of the serogroup B isolates tested. The analysis demonstrated durability between 

subfamilies, as well as surface expression of FHbp. In a subset of isolates for which 

bactericidal activity was assessed, isolates with moderate or high level of expression of FHbp 

was predictive of bactericidal activities; whereas, there was a lower correlation among isolates 

with low expression of FHbp [Jiang et al., Vaccine 28 (2010) 6086-6093]. 

For the Novartis vaccine, MenB-4C, the Meningococcal Antigen Typing System (MATS) was 

used to estimate coverage. MATS is a sandwich enzyme-linked immunosorbent assay (ELISA) 

that measures cross-reactivity with vaccine antigens, as well as a level of expression of each 

antigen to predict bactericidal activity against a broad number of strains. In order to assess the 

immunogenicity of each antigen, four of the primary strains were selected based on having 

cross-reactivity with 1 vaccine antigen while having limited cross-reactivity with other vaccine 

antigens, and thus were not representative of circulating strains in the US. MATS was 

previously bridged to serum bactericidal activity using human complement (hSBA) in a subset of 

antigenically diverse strains and was found to be greater than 80% predictive of bactericidal 

activity when one antigen was expressed above a certain threshold, and greater than 90% 

when at least two antigens were expressed above a certain threshold. Based on the analysis of 

over 400 US isolates, MenB-4C is estimated to cover 91% of circulating strains in the US 

[Donnelly et al., PNAS (2010) vol. 107, no. 45. Based on a representative strain panel of 

invasive MenB isolates from 2000-2008 selected by US CDC (adjusted with respect to strains 

from Oregon)]. 

In summary, true breadth of coverage of endemic MenB disease has only been estimated for 

these two vaccines. The manufacturers have used two different methods to assess the breadth 

of coverage for their vaccines, and secondary studies to evaluate immunogenicity against 

additional strains are pending. 

These are the five outcomes for consideration in the GRADE analysis: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The data sources included published and unpublished data, as well as information from the 

investigator’s brochure. Studies conducted in US and non-US populations were included as 

long as the final formulation and the manufacturer’s proposed dosing for the vaccine was used. 

Due to the low incidence of serogroup B meningococcal disease, an efficacy trial using clinical 

endpoints was impractical. Therefore, vaccine efficacy estimates were based on the 

demonstrations of a functional immune response in recipients against a small number of 

serogroup B strains. In studies supporting US licensure, immunogenicity was assessed by the 

proportion of subjects who achieved a greater than or equal to four-fold increase in hSBA titers 

for each of the strains tested, and the proportion of the subjects who achieved a titer greater 

than or equal to the lower limit of quantitation of the assay for all strains, referred to as the 

composite response. The lower limit of quantitation was defined as the lowest amount of 

antibody in a sample that can be reliably quantified. Although the licensure endpoints are the 

same, data from MenB-FHbp and MenB-4C are not directly comparable because, for example, 

the persons were each tested against different serogroup B strains. 

As a reminder, the criteria used for GRADE analysis are as follows: 

 Risk of bias (methodological limitations) 

 Inconsistency 

 Indirectness 

 Imprecision 

 Other considerations (publication bias, strength of association, dose gradient) 

The following algorithm is used to determine the final evidence type for each outcome: 

Randomized controlled trials (RCTs) begin as an evidence type of 1, and observational studies 

begin as 3. The five criteria are assessed to determine whether the evidence type is moved up 

or down. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

In terms of the evaluation of these outcomes for Bexsero®, MenB-4C, there were five studies 

including one non-controlled, open-label study and four RCTs. The majority of the studies 

assessed multiple outcomes. Four of the studies have been published. However, the WG also 

assessed unpublished data where available. In addition, the WG reviewed severe adverse 

events (SAE) for post-vaccination data. No studies assessing safety and immunogenicity with 

concomitant vaccine have been completed. 

For evidence of benefits, short-term immunogenicity after a two-dose series ranged from 63% 

to 94%, depending upon the study. Persistence was measured 11 to 24 months after 

vaccination with the two-dose series and ranged from 66% to 94%, depending upon the study. 

For evidence of harms based on SAEs, of all the studies assessed, a total of 3140 participants 

received at least one dose of the vaccine. Among the vaccine subjects, 67 SAEs were 

reported. In most cases, the SAE rate was similar between the MenB vaccine group and other 

groups within each study. Five SAEs were considered related to MenB vaccines, and no 

concerning pattern was observed among these SAEs. Two deaths unrelated to the vaccine 

were reported in one of the studies. Review of SAE surveillance data from vaccination 

campaigns conducted in Princeton, Santa Barbara, and Quebec showed that of the 59,000 

participants who received at least one dose of the vaccines, 60 SAEs were reported and three 

SAEs were considered related to the vaccine. All three SAEs resolved over time. One death 

was reported, but was determined to be unrelated to the vaccine. 

For risk of bias, the WG downgraded the persistence in immunogenicity outcome by 1 due to 

potential selection bias and unplanned sample size determination. For consistency, the WG 

downgraded the short-term immunogenicity outcome by 1 due to high heterogeneity between 

studies. For indirectness, the WG downgraded short-term immunogenicity and persistent 

immunogenicity outcomes by 1 each for indirect assessment of vaccine efficacy. For 

imprecision, the WG downgraded SAE outcomes by 1 because the confidence interval around 

the effect estimates includes effect and non-effect. The short-term immunogenicity outcome 

was upgraded by 1 for the strong strength of association. The overall evidence type is 2 for 

short-term immunogenicity, 3 for persistence immunogenicity, and 2 for the two SAEs. Safety 

and immunogenicity following concomitant vaccination was not assessed. 

The following table summarizes the balance between benefits and harms, as well as the 

evidence type: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Regarding the evidence type of Trumenba®, MenB-FHbp, there were seven studies including 

two non-controlled studies and five randomized-controlled studies. The majority of studies also 

assessed multiple outcomes. Three of the studies have been published. Non-published data 

were also reviewed from these studies. For evidence of benefits, short-term immunogenicity 

measured one month after a three-dose series ranged from 80% to 81%, depending upon the 

study. Based on non-inferiority criteria, no immunologic interference was observed for 

MenACWY, Tdap, TdaP/IPV, or HPV types 6,11,16. Persistence was measured at the 48th 

month after vaccination with the three-dose series and demonstrated protective titers against 

three of the four primary strains in more than 50% of the subjects. 

For evidence of harms, a total of 11,338 participants received at least one dose. SAEs were 

reported among subjects. In most cases, SAE rates were similar between vaccine groups and 

other groups in each study. Seven SAEs were considered related to MenB-FHbp. No 

concerning pattern was observed among these events. One death unrelated to the vaccine 

was reported. For risk of bias, the WG downgraded persistence in immunogenicity outcome by 

1 due to its very small sample size. For indirectness, the WG downgraded short-term 

immunogenicity, persistence in immunogenicity, and MenB immunogenicity with concomitant 

vaccination each by 1 each due to indirect use of correlate of immunogenic endpoints to 

measure efficacy. For imprecision, the WG downgraded both SAE outcomes by 1 each 

because the confidence interval around the effect estimate includes both effect and non-effect. 

Short-term immunogenicity was upgraded by 1 due to the strong strength of association. The 

overall evidence type turned out to be 2 for short-term immunogenicity, 4 for persistence in 

immunogenicity, 2 for MenB immunogenicity with concomitant vaccination, and 2 for both SAEs. 

The following table summarizes the balance between benefits and harms, as well as the 

evidence type: 

The following table summarizes the evidence type for both vaccines graded: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Considerations for Routine Use of MenB Vaccines in Adolescents 

Jessica MacNeil, MPH 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Ms. MacNeil presented a summary of the WG’s considerations for use of serogroup B 

meningococcal vaccines in adolescents. She summarized the data reviewed by the WG, and 

presented the policy options and the WG’s considerations for use of MenB vaccines in 

adolescents and the proposed policy option language for this session’s vote. 

In the US, the incidence of meningococcal disease is currently at an historic low. In 2013, a 

total of 564 cases of meningococcal disease were reported. Declines in incidence have been 

observed for all of the serogroups, including serogroup B, which is not included in the 

meningococcal conjugate vaccines. In addition, despite steady increases in coverage with 

conjugate vaccine among adolescents, much of the decline in incidence occurred prior to high 

levels of coverage in adolescents. In 2013, coverage with one or more doses of conjugate 

vaccine was estimated to be 77% among those 13 through 17 years of age, but varied from 

40% to 94% by state. Two-dose series completion was estimated to be less than 30%. As the 

current adolescent program has become more established, the first impact of the program on 

rates of serogroup C/Y/W meningococcal disease has been observed. The combined incidence 

of C/Y/W has decreased by 80% from 2004 to 2005 to 2012 to 2013 among those 11 through 

19 years of age. The same decline in incidence has not been observed among persons in age 

groups that are not routinely receiving conjugate vaccines, including infants less than one year 

of age and persons 20 years of age and older. Incidence in adolescents and young adults is 

similar for serogroup B and serogroups C and Y combined. The remaining burden of 

serogroups C and Y disease in this age group highlights the need for additional efforts to 

reinforce the importance of the second dose of the conjugate vaccine in the current adolescent 

program. 

In terms of annual cases, deaths, and cases that result in long-term sequelae from serogroup B 

and serogroups C and Y meningococcal disease, it is estimated that in recent years, serogroup 

B has caused approximately 55 to 65 cases annually in those 11 through 24 years of age. 

Approximately 80% of those cases occurred in older adolescents and young adults 16 through 

24 years of age. In the US, approximately 61% of those 18 through 23 years of age enroll in 

college. Information on college attendance for meningococcal cases is collected through ABCs, 

but is not collected through NNDSS. In recent years, approximately 40% of serogroup B cases 

among those 18 through 23 years of age reported to ABCs attended college. That proportion 

can be applied to serogroup B cases reported to NNDSS in this age group to estimate the 

number of meningococcal cases occurring in college students nationwide. 

From 2009 through 2013, there were an estimated 14 cases of serogroup B meningococcal 

disease in college students annually, with two deaths in this age group. The incidence of 

serogroup B meningococcal disease among college students was similar to the incidence 

among all 18 through 23 year olds and to non-college students. Although a similar risk is 

estimated for serogroup B meningococcal disease in college students and non-college students 

in this age group, seven clusters or outbreaks of serogroup B meningococcal disease have 

been reported to CDC from university campuses since 2009, including two since the beginning 

of 2015. As a result of these outbreaks, the number of surveillance sites reporting information 

on college attendance was expanded in order to better track the burden of disease in this 

group. 

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Beginning in 2013, enhanced surveillance was established for cases of meningococcal disease 

among college students in an area which covers approximately 60% of the US population. In 

2013 and 2014, approximately 65% of serogroup B cases among 18 through 23 year olds in 

these sites have been reported in college students, with two deaths reported each year. 

However, even with the enhanced surveillance sites collecting additional information on cases 

occurring in this population, there are years during which more cases and deaths occur. For 

example, in 2014 three deaths from serogroup B meningococcal disease in college students 

were reported to CDC, one of which occurred outside of the enhanced surveillance area. 

To summarize, the US is currently experiencing a historic low in meningococcal disease 

incidence. The incidence of disease has declined for all meningococcal serogroups, including 

serogroup B, which is not included in the conjugate vaccines. For the last several years, the US 

has remained at a stable low in disease incidence, with approximately 55 to 65 cases of 

serogroup B meningococcal disease reported in adolescents and young adults each year. The 

majority of serogroup B cases in adolescents occur in older adolescents and young adults 16 

through 24 years of age. Approximately 40% to 70% of serogroup B cases in 18 through 23 

year olds occur in college students. However, incidence in both college and non-college 

students is similar. 

Regarding the immunogenicity data for the MenB vaccines, there are two serogroup B 

meningococcal vaccines licensed in the US for use in persons 10 through 25 years of age as 

previously noted. MenB-FHbp contains both subfamilies of FHbp and is administered as a 

three-dose series. MenB-FHbp was licensed by the Food and Drug Administration (FDA) in 

October 2014. MenB-4C contains four components and is administered as a two-dose series. 

MenB-4C was licensed for use in the US by FDA in January 2015, and is also licensed in a 

number of other countries for use in persons two months of age and older. 

As reported by Dr. Folaranmi, vaccine efficacy was estimated from serum bactericidal 

antibodies against a small number of serogroup B strains. In studies supporting US licensure, 

immunogenicity was assessed by both the proportion of subjects who achieved a greater than 

or equal to four-fold increase in hSBA titer for each of the strains tested and a proportion of 

subjects who achieved a titer greater than or equal to the lower limit of quantitation of the assay 

for all strains, or the composite response. Although licensure endpoints are the same, data 

from MenB-FHbp and MenB-4C are not directly comparable. The complete immunogenicity 

and safety data that supported licensure of MenB-FHbp was presented by Pfizer during the 

October 2014 ACIP meeting. To summarize, MenB-FHbp has a demonstrated immune 

response in the general adolescent population. Of the subjects, 84% had a composite hSBA 

response to four strains after three doses, and 50% had a composite response after two doses. 

Data on concomitant administration of MenB-FHbp and the other adolescent vaccines is 

reassuring. No immunologic interference was observed for serogroup B or vaccine antigens 

including HPV types 6/11/16, MenACWY, TdaP, and IPV antigens. For HPV type 18, noninferiority criteria were not met for the geometric mean titer (GMT) ratio at one month after the 

third quadrivalent HPV vaccination. However, 99% of subjects achieved seroconversion for all 

four HPV antigens. Antibody persistence data through 48 months post-dose 3 from MenBFHbp was recently presented to the WG. The proportion of subjects with hSBA titers > 1:4 

peaks at one month following the third dose for all four strains tested. For Strains A22 and B24, 

which represent more prevalent FHbp subvarients in the US, the proportion of subjects with 

protective titers falls quickly to approximately 60% by six months following the third dose, but 

then remains stable through 48 months post dose 3. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Immunogenicity and safety data for MenB-4C were also presented during the October 2014 

ACIP meeting. Immunogenicity data from the three main trials conducted in Canada-Australia, 

the UK, and Chile were used to assess the effectiveness of MenB-4C. Of the subjects, 63% to 

94% had a composite hSBA response to three strains after two doses. The immunogenicity 

data from the Canadian-Australian study conducted in adolescents 11 through 17 years of age 

was included in the package insert because the hSBA responses generated by the study 

participants were more likely representative of the responses in the US population as compared 

to the Chilean study, which also enrolled adolescents 11 through 17 years of age. The UK 

study, conducted in young adults between the ages of 18 and 24 years of age, was also 

included in the package insert to provide data on young adults 18 through 25 years of age. 

Antibody persistence following two doses of MenB-4C has been examined in two of these 

studies. Of subjects in a study among UK university students, 66% maintained a composite 

hSBA response to the three strains 11 months post-dose 2. Among Chilean adolescents, 77% 

to 94% maintained an hSBA response > 1:4 18 to 24 months post-dose 2. However, prevaccination hSBA titers were also higher in the Chilean adolescents compared to what is 

expected for the US population. No concomitant administration data are available for MenB-4C. 

Recently, preliminary results from a seroprevalence survey conducted at Princeton University 

by Nicole Basta were also shared with the WG. As a reminder, between March 2013 and 

March 2014, nine cases of serogroup B meningococcal disease occurred in persons linked to 

Princeton University, including one death. Laboratory-typing results were identical for the A 

isolates that were available, and all were ST-409, which is uncommonly seen in the US. A 

mass-vaccination campaign using MenB-4C was held in December 2013, and a second-dose 

campaign was held in February 2014. Smaller catch-up campaigns were held following each 

mass clinic. Overall, coverage among undergraduates by the end of the vaccination campaigns 

was 98% for the first dose and 93% for the second dose. A cross-sectional seroprevalence 

survey was launched in April 2014, and 607 participants were enrolled. Focusing on the largest 

group of subjects who received both doses during the mass clinics in December and February, 

approximately 66% of subjects had an hSBA titer > 1:4 against the outbreak strain in April 2014, 

two months after the second dose of MenB-4C. From the original 607 participants, a subset of 

245 samples were selected to assess immune response against one of the vaccine strains. 

Nearly all subjects who received two doses of MenB-4C had hSBA titers > 1:4 against the 5/99, 

or NadA, vaccine reference strain. In addition, GMTs were much higher for the vaccine 

reference strain compared to the outbreak strain [Basta et al. Immunological Response 

following the Introduction of a Novel Meningococcal B Vaccine during an Outbreak at a 

University in 2013-2014. In preparation]. 

To summarize the WG’s interpretation of the available immunogenicity data, immunogenicity 

studies predict efficacy of the MenB vaccine in the short-term. However, there is evidence of 

waning antibody levels within six months post-dose 3 for MenB-FHbp, and there appears to be 

modest antibody waning observed through 24 months post-dose 2 for MenB-4C. In addition, in 

the Princeton study, the proportion of responders to the outbreak strain appeared to be lower 

than to the vaccine reference strain, which highlights that the proportion of vaccinees who 

develop bactericidal antibodies protective against each outbreak or circulating strain may differ. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Regarding safety data for the MenB vaccines from clinical trials, post-vaccination local and 

systemic complaints are common. The most frequently reported solicited adverse events (AEs) 

were pain at the injection site, fever, headache, fatigue, myalgia, and arthralgia. Reactions 

were typically self-limited and resolved within three to seven days. The MenB vaccines were 

more reactogenic than other routine vaccines for adolescents based on the proportion of 

subjects who report the most severe category of local and systemic adverse events. Rates of 

SAEs reported in the clinical trials were similar between vaccine recipients and controls. 

There is some limited experience with the safety of MenB vaccines outside of clinical trials. 

Most of the experience is with MenB-4C, which was administered to approximately 17,000 

persons vaccinated under an expanded access IND program for outbreak response at two US 

universities and over 40,000 persons vaccinated in a regional public health program in Quebec. 

No concerning patterns among the AEs were observed following any of these vaccination 

programs. For MenB-FHbp, safety data were collected during one of the recent outbreak 

response; however, those data are not yet available. 

The WG also reviewed data from animal models that showed auto-antibodies in some animals 

following MenB vaccination1-3, which raises theoretical concerns about the development of autoimmune disorders. FDA reviewed the clinical data and did not observe differences in rates of 

auto-immune disorders between vaccine recipients and controls. The data do not suggest a 

higher incidence of autoimmune conditions following vaccination than what is observed in the 

general population. Theoretically, onset of auto-immune symptoms could be delayed well 

beyond vaccination. Post-licensure safety surveillance will be conducted to detect any potential 

safety signals. However, this will require a large number of doses to be administered to be able 

to detect any potential safety signals in the Vaccine Safety Datalink (VSD). In the meantime, 

Vaccine Adverse Event Reporting System (VAERS) reports will be monitored [1

Costa I, et al. 

mBio. September/October 2014; 5(5): e10625-14. 2

Granoff D. 2014. Microbe. 9(8):321-327. 

3

Granoff D. JID. 2015]. Adverse reactions may occur following any type of vaccine. Shoulder 

injury related to vaccine administration has been recognized in case reports. The incidence is 

unknown, though it appears to be very rare. Syncope occurs at a rate of about 1 per 1000 

doses and can lead to injuries from falling. Anaphylaxis may also occur following any type of 

vaccine and occurs at a rate of 0.21 to 1.53 per 1 million doses administered. MenB-FHbp and 

MenB-4C have each had one case of anaphylaxis reported to date. 

The WG’s interpretation of the MenB safety data is that post-vaccination local and systemic 

complaints are common following MenB administration, but the reactions are typically selflimited. The most common AE reported was pain at the injection site. Potentially serious AEs 

may occur following any vaccine, and should be considered in light of the current low disease 

burden. To date, no concerning patterns of SAEs have been reported for MenB vaccines. 

However, theoretical concerns have been raised from animal models about autoimmune 

disorders and will need to be monitored through post-licensure safety surveillance. 

The WG also considered additional data. A cost-effectiveness analysis for routine use of 

serogroup B meningococcal vaccines was completed by Ismael Ortega-Sanchez of CDC. The 

full presentation was included in the ACIP members’ background materials. This was a Monte 

Carlo simulation analysis for a hypothetical 4 million person birth cohort and a 2.8 million 

college cohort. The timeframe for the analysis was 15 years. The analytic horizon was agespecific life expectancy. The discount rate was 3% (0%-5%). Key assumptions of the analysis 

included age and serogroup B-specific average incidence rates and case-fatality ratios from 

1994 through 2013, and initial vaccine effectiveness of 85% to 95%, waning protection was 

modeled based on available antibody persistence data for MenB-FHbp and MenB-4C with 

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waning of protection over 10 years, and a vaccine cost per series (2 or 3 doses) of $402 (cost of 

vaccine + administration + AE + wastage). It is estimated that approximately 15 to 30 cases 

and 2 to 5 deaths could be prevented with a routine adolescent program at 11, 16, or 18 years 

of age. A college student only recommendation would prevent approximately 10 cases and 1 

death. The number needed to vaccinate (NNV) to prevent either a case or a death is high. 

Nearly 100,000 to 400,000 persons would need to be vaccinated to prevent one case. Nearly 1 

to 3 million persons would need to be vaccinated to prevent a death. The cost per quality 

adjusted life years (QALY) saved ranged from approximately $4 million to $9 million dollars in 

this analysis. 

Currently, limited data are available on the impact of the MenB vaccines on carriage. In a study 

conducted in a university in the UK, 31% to 34% of subjects carried any Neisseria meningitidis 

at study entry. No significant difference in carriage was detected between the study groups at 

one month after vaccination with MenB-4C. However, a modest decrease in carriage was 

observed during the 12 months after vaccination. In the US, two carriage surveys were initiated 

in February of 2015 at schools experiencing serogroup B outbreaks. The surveys are being 

conducted in conjunction with MenB-FHbp mass-vaccination campaigns at these schools. 

Baseline carriage was assessed during administration of the first dose, and post-dose 1 

carriage was assessed during the second dose mass-vaccination clinics. Additional rounds of 

the carriage study are planned for Fall 2015 at both schools. Preliminary results from studies 

showed no change in carriage in the student population from baseline to post-dose 1. 

Another important consideration for the use of MenB vaccines is breadth of coverage. Genetic 

and antigen expression data predict that the MenB vaccines should cover a wide range of 

circulating meningococcal strains in the US, but they will not cover all strains. The 

immunogenicity data currently available are directed against a few select strains. However, 

testing against additional strains is planned as part of a post-licensure commitment to FDA by 

both manufacturers. However, the proportion of the population who will respond to each 

circulating strain is currently unknown. One example of this is the lower responses that were 

observed to the Princeton outbreak strain. The currently available data do not allow for 

prediction of the proportion of the population who will respond for each outbreak or a sporadic 

disease-causing strain. 

In summary, there are a number of challenges to keep in mind when considering the use of 

MenB vaccines in the US. First, the proportion of serogroup B cases that could be prevented 

with a MenB vaccine is unknown. Breadth of strain coverage has only been estimated. The 

actual breadth of coverage is unknown or unclear. Available antibody persistence data suggest 

that MenB vaccines may have a limited duration of protection. In addition, vaccine 

effectiveness data are not yet available, as licensure was based on serum bactericidal activity 

and universal programs have not yet been implemented in any country. The potential impact of 

the MenB vaccines on carriage is also unknown, as is the potential impact that the vaccine 

pressure will have on circulating strains. 

The WG has considered several policy options for broader use of MenB vaccines in 

adolescents. Ages for the recommended administration of a MenB vaccine series that were 

considered included at 11 to 12 years with an anticipated booster at 16 years of age, or a series 

at 16 or 18 years of age, or a recommendation for college students only. In addition, the WG 

considered different recommendation types, including Category A, which is a recommendation 

for all persons in an age- or risk-factor-based group; Category B, which is a recommendation 

made for individual clinical decision-making; or no recommendation. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

After reviewing the data, the consensus of the WG was to support a policy option that included 

vaccination of all adolescents rather than college students only. The WG’s considerations 

included that an important burden of serogroup B meningococcal disease cases occur in those 

18 through 23 years of age who are not attending college. It would be challenging to get 

students vaccinated with two or three doses before arriving on college campuses, and 

vaccination of college students would prevent the fewest cases and deaths among the options 

considered. However, the WG also acknowledged the impact that cases and outbreaks have 

on college campuses in terms of the cost of vaccination campaigns in response to these 

outbreaks and public concern. 

The WG considered three options for the preferred timing of the MenB series, including at 11, 

16, or 18 years of age. Based on the available antibody persistence data, the WG felt that 

there was a need to administer the MenB vaccine series in later adolescence, preferably at age 

18, in order to maximize the likelihood that protection would last into the highest risk period. 

However, the WG also recognized that young adults may still be under the care of a pediatrician 

at 16 years of age, but will be less likely to receive care from their pediatrician at age 18. They 

should also be making a visit to their healthcare provider at age 16 for the MenACWY conjugate 

booster. Based on these considerations, the majority of the WG members preferred language 

recommending administration between 16 and 18 years of age. This will also increase the 

likelihood that the college-bound population will complete the two- to three-dose series before 

entering college during the highest age-related risk period. 

The WG currently favors a Category B rather than a Category A recommendation for two main 

reasons. First, the current burden of diseases is low. This means that the NNV to prevent a 

case and death is high, and the number of cases prevented may be comparable to the number 

of SAEs to vaccine. Second, additional data are still needed to consider a routine 

recommendation. Most importantly, a better understanding is needed of the true proportion of 

serogroup B cases that could be prevented with MenB vaccine, including data on vaccine 

effectiveness and the impact of MenB vaccines on carriage and herd immunity. 

The WG recognizes that historically, Category B recommendations for use of polysaccharide 

vaccine in college students was unpopular and was interpreted as difficult to understand. The 

2000 recommendation was that college students and their parents be informed by healthcare 

providers of the risks of meningococcal disease, and the potential benefits of vaccination with a 

polysaccharide vaccine. College and university health services were also to facilitate 

implementation of educational programs about meningococcal disease and the availability of 

vaccination services. Polysaccharide vaccine was to be made available to those persons 

requesting vaccination. In several states, this Category B recommendation was translated into 

legislation requiring colleges to provide information on the risks of meningococcal disease to 

students or mandate vaccination of certain students. 

Finally, there are additional programmatic considerations which the WG discussed such as 

implementation challenges of a MenB multi-dose vaccine schedule, and that there is no 

platform for a two- or three-dose vaccine series in late adolescence. The current MenACWY 

vaccine program in adolescents is at 11 to 12 years of age with a booster at 16 years of age, 

which makes communication challenging when there are differing recommendations for the 

conjugate vaccine and the MenB vaccines. MenACWY is not currently recommended for other 

groups with similar or higher risk, but that may need to be reconsidered if a Category B 

recommendation is made for MenB in adolescents. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

In summary, the Meningococcal WG acknowledged that meningococcal disease is a rare but 

serious illness and each case is life-threatening. However, important data for making policy 

recommendations for MenB vaccines are not yet available. There was a strong desire within 

the WG to ensure access to MenB vaccines, as well as an understanding that work still needs 

to be done to reinforce the second dose of the conjugate vaccine in the current adolescent 

program. The risk of meningococcal disease is low. However, cases do occur. It is difficult to 

accept that, in the absence of a vaccination program, there may be cases that are preventable. 

However, even with a fully implemented vaccination program, the MenB vaccines will not 

prevent all cases. 

The WG proposed the following language for use of MenB vaccines in adolescents: 

“A serogroup B meningococcal (MenB) vaccine series may be administered to 

adolescents and young adults 16 through 23 years of age to provide short term 

protection against most strains of serogroup B meningococcal disease. The preferred 

age for MenB vaccination is 16 through 18 years of age. (Category B)” 

In addition, the following language would be provided as guidance for use: 

 MenB should be administered as either a 2-dose series of MenB-4C or a 3-dose series 

of MenB-FHbp 

 The same vaccine product should be used for all doses 

 Based on available data and expert opinion, MenB-4C and MenB-FHbp may be 

administered concomitantly with other vaccines indicated for this age, but at a different 

anatomic site, if feasible 

 No product preference to be stated 

Discussion Points 

Dr. Belongia noted that in the MenB-4C trial, there was an episode of thyroiditis and two 

episodes of juvenile rheumatoid arthritis (RA) that were thought to be vaccine-related. He 

wondered if anyone had any information regarding why that was thought to be the case. Given 

that the vaccine is licensed in multiple other countries, he wondered whether there were any 

post-licensure data on safety from other countries that could help to understand potential risks. 

Ms. MacNeil responded that currently, there are not post-licensure safety data available from 

other countries. The vaccines are licensed in several other countries, but no programs have 

been implemented. The United Kingdom (UK) plans to begin vaccinating infants in September 

2015, after which there will be more information. 

Noting that ACIP tends to avoid Category B recommendations, Dr. Harrison asked what the 

potential impact of a Category B recommendation would be on cases, deaths, and college 

outbreaks prevented. For a disease with a relatively high case fatality rate, his sense was that 

a Category B vaccine probably should be avoided. 

Ms. MacNeil replied that a lot depends upon the extent of vaccine uptake and how much 

coverage there is in the population, which is unknown at this point. There may be mandates or 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

recommendations for college students to be vaccinated. While that is likely to vary by individual 

school, coverage probably will be highest in those groups. 

Dr. Temte invited Dr. Even to make a comment regarding what role residential colleges and 

universities would have, and the likelihood that they would either mandate or strongly 

recommend a vaccine. 

Dr. Even (ACHA) indicated that vaccinations can be mandated upon school entry. In general, 

her observation and experience has been that private universities have a wider range of 

recommendations that perhaps mirror CDC and ACIP recommendations for college-aged 

students. This varies broadly among smaller and public universities. Some of them will select 

certain immunizations for requirement. With a Category B recommendation, a mandated 

requirement is less likely, but it would probably be part of information campaigns. 

Dr. Reingold noted that Slide 3 showed the incidence rates for various meningococcal 

serogroups, with the declines being indistinguishable for B and the serogroups in the 

A/C/Y/W135 vaccine. However, Slide 4 showed compelling evidence that a decline in 

A/C/Y/W135 is limited to the group targeted for vaccination, which was an interesting distinction 

that was difficult to understand and he wondered whether there was an explanation for that. He 

also said he was very happy that the workgroup did not opt for a college-only recommendation, 

given that primarily those who are better-off go to college in this country, which creates an 

equity issue. To him, the only reason to focus on a college-only recommendation would be if 

the rate of disease was substantially higher and it clearly is not. 

Ms. MacNeil responded that while there have been many theories, the reason is unknown why 

meningococcal disease rates have continued to decline in the population overall. 

Ms. Pellegrini asked for clarification regarding the workgroup’s consideration of the dosing 

schedules beginning at age 11 or 12, and whether that would be two or three doses followed by 

a booster dose at age 16. The problem is that there is not a platform for late adolescence. 

Getting any teenager into the doctor more than once a year is difficult. Getting a 17- or 18-year 

old is likely to result in poor compliance rates. 

Ms. MacNeil clarified that it would be a complete series at 11 or 12 years of age. While no data 

are available yet, it is anticipated that based on antibody persistence, a booster would be 

needed at 16 years of age. It would be an additional dose. 

Dr. Loehr (AAFP) pointed out that if his calculations were correct, there are about 50 to 60 

cases in persons 18 through 24 years of age. In a cohort of about 4 million per year, that is 

about 1 in a million incidence rate. The rate of anaphylaxis is about 0.2 to 1.5 per million doses, 

and both small studies already each had one case of anaphylaxis. That is, there was one case 

of anaphylaxis in the study with 11,000 and one case in the study with 60,000. Extrapolating 

those would indicate that there is possibly a higher rate of anaphylaxis than for other vaccines, 

based on the available data. That would mean a 1 in a million case incidence and between 17 

to 100 cases of anaphylaxis per million. 

Ms. MacNeil confirmed that this is what has been observed. However, she did not believe there 

was enough information to say that rates are higher for these vaccines at this point. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Regarding the policy option and the issue of strain diversity, Dr. Karron wondered with what 

confidence it could be said that short-term protection against most strains of serogroup B 

meningococcal disease differ between vaccines. 

Ms. MacNeil replied that this is not known for sure. Though tested against only a few strains, 

the assumption is that a majority of serogroup B strains in the US would be covered. 

It appeared to Dr. Gorman (NIH) the recommendation language would exclude 75% of the 

cases of serogroup B from potential protection. Recommending that individuals 16 through 18 

years of age be vaccinated permissively, to use old language, that would be 54 out of the 203 

or 67 out of the 260. He wondered what drove the recommendation for that particular age 

range. 

Ms. MacNeil indicated that 80% of cases are occurring in individuals 11 through 24 years of 

age, with most cases in that age group actually occurring in adolescents 16 through 24 years of 

age. That was part of the rationale for the recommendation at the later age. There are very few 

cases among those 11 through 15 years of age. 

Dr. Gorman (NIH) wondered why the recommendation was not for less than 5 years of age 

where there are more cases. 

Ms. MacNeil responded that the vaccine is not licensed in that age group. 

Dr. Temte reiterated that there is currently no FDA licensure for revaccination. The vaccines 

are licensed for two or three doses. He asked whether manufacturers were planning to conduct 

studies pertaining to revaccination. 

Laura York (Pfizer) indicated that Pfizer has ongoing studies. They will be boosting individuals 

who received vaccine about four years ago. Those data are anticipated to be available in 2016. 

Leonard Friedland (GSK) indicated that GSK’s current attention is focused on a pentavalent 

meningococcal ACWYB combination vaccine. With that vaccine, booster doses will be studied 

as well. 

Dr. Harriman pointed out that cost-effectiveness analyses must be considered with caution, 

especially when performed before the widespread use of a vaccine because it is known that the 

cost can increase or decrease. It is also known that cost-effectiveness analyses favor common 

but less severe diseases over rare but very severe diseases. The public shows a preference 

for trying to protect against rare but severe diseases. She would like to have seen some 

analyses with price points other than the manufacturers’ retail prices. Presumably, the UK is 

receiving a much less expensive vaccine. Cost-effectiveness analyses are extremely sensitive 

to both cost and incidence. She would like to see better incidence data as well. While she is 

happy that ACIP has a Category B recommendation that does get paid for, she worries that it 

may be perceived as a less important vaccine and may not be offered or recommended as 

often. It is very difficult to explain to a parent whose child has died of meningococcal B disease 

why a vaccine was available but was not recommended for their child. 

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Dr. Temte noted that this reflected the GRADE process in that after the evidence evaluation in 

trying to formulate recommendations into a Category A or B or no recommendation, costeffectiveness is used. As Dr. Loehr pointed out, the balance of benefits and harms are 

assessed in terms of potential adverse effects. Consideration also is given to the values and 

preferences of stakeholders, liaisons, and the general public. It is good, with the known 

unknowns and unknown unknowns, with this vaccine going forward to have a variety of options 

there in terms of making recommendations. 

Dr. Kempe emphasized that given the potentially small benefits, potential risks must be 

considered very carefully. She would like to know more about why the cases of thyroiditis and 

RA were related to the vaccine. 

Dr. Schuchat indicated that CDC did not have more details on that, but the manufacturers may 

have those data. 

Dr. Friedland (GSK) did not have further information about the three cases. GSK has been 

following over 45,000 patients in post-marketing studies for vaccines that have been used 

inside and outside of the US. No signals have been observed related to the concern about 

autoimmunity. They will continue to follow this very closely in all of the trials throughout the 

world. 

Dr. York (Pfizer) stressed that this is always a concern, particularly in the adolescent population. 

Under Pfizer’s clinical trial, the FDA reviewed all of the data that were available and did not see 

a signal. 

Dr. Baker (IDSA) pointed out that the problem is the denominator. It is unknown whether this is 

going to stay flat for 3 million people versus 3,000 or 11,000. The beauty of Category B is that 

there are two FDA-licensed vaccines, and the appeal to her is that individual physicians or 

parents or of-age young adults can have a discussion regardless of whether they are under the 

VFC program or would not have the funds to pay for the vaccine out of pocket. As noted 

earlier, this age group is not necessarily attending college, so the equity issue is addressed 

through a Category B recommendation. 

Dr. Temte emphasized that a Category B recommendation automatically falls under the VFC 

and the ACA. A Category A or B recommendation avoids creating inequity. Alternatively, 

making no recommendation creates a situation in which people who can afford the vaccine can 

get it and those who cannot afford it will choose not to get it. 

Dr. Moore (AIM) stressed that there are many unknowns regarding how well this vaccine is 

going to perform. Regarding the spread of the short-term immunogenicity results in the RCTs, 

she was perturbed by seeing 63% to over 90%. She wondered if there was a biologic 

explanation for such a spread in those results. From a programmatic standpoint, AIM will be 

considering how to implement Category B recommendations and how they are presented in 

IISs. From the program standpoint, they want to try to understand how best to convey the 

intention of the committee in terms of vaccine forecasting with IISs. What will they say when a 

16-year-old comes in? Should it be left off of the forecasted recommendation list, or listed 

somehow differently? It is not clear yet how to show that a Category B is a permissive 

recommendation. 

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Ms. MacNeil indicated that the data from the hSBA came from three strains or four strains. On 

the higher end, some of the studies were conducted in populations in which the epidemiology is 

quite different from in the US. For example, about 20% of the people had a baseline titer, which 

probably indicates high levels of carriage. Some may have had some pre-existing immunity, 

which may increase that. Compared to populations that are more similar to the US, it is 

somewhat lower. 

Dr. Grogg (AOA) reminded everyone that as a practicing clinician who receives calls in the 

middle of the night during influenza season and the rapidity of the illness of meningococcal 

disease, he feels much better counseling patients if he knows they have had a meningitis 

vaccine and are current on all vaccinations when a 102o temperature and muscle aches are 

reported. 

Regarding the persistence data, Dr. York (Pfizer) emphasized that there are differences in 

populations. The backgrounds can make a difference in terms of the actual results and the way 

those results are presented. The approaches that are taken to show breadth of coverage or the 

response to the vaccination antigen will, perhaps, make an impact on that. Pfizer’s approach is 

to assess the response over time in a study that started in a number of countries very early in 

order to assess the responses that are predicted in various populations. In the data from a 

number of studies in different countries, the range of responses against the four strains that are 

representative are very consistent. Therefore, they believe the persistence will be consistent. 

Dr. Schuchat pointed out that the short-term immunogenicity results differed not only by country 

or study, but also by the populations which were different ages. She wondered within the 

studies if there were any age-related differences in the short-term immunogenicity. The UK had 

the highest results, but they had the older population. 

Ms. MacNeil did not think specific age-related differences were assessed within the different 

populations. The reason that the UK study was included in the package insert was because it 

had data for older adolescents; whereas, no other study was conducted in the age group. The 

Canadian and Australian data were included as well for the younger age group because they 

were thought to be the most representative of US populations. 

Ms. Pellegrini noted that the debate was crystalizing for her the challenges associated with 

conversations that were also occurring in the health policy world pertaining to the differences 

that exist in the types of data that are necessary for FDA licensure versus an ACIP 

recommendation. While she understood the tremendous challenge for drug makers to try to 

prognosticate what the data are and how to acquire it, with the more frequent use of the FDAexpedited pathways and alternative pathways for approval, this is going to be an increasing 

issue with vaccines in the future. 

Dr. Paradiso (Vaccine Consultant) reminded everyone that a composite response rate meant a 

response to all of the strains tested. A response rate of 90% for each strain means that by the 

fourth strain, it is 90% of 90% of 90% of 90%. It is not going to be 90% of a composite. He was 

hearing some push and pull on the A and B category, with a leaning toward the B category and 

the hope that people will still use the vaccine. He heard the question regarding whether 

colleges would mandate the vaccine or recommend use with a Category B recommendation, 

with the hope that they would. However, a B category recommendation would make that less 

likely to occur. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Zahn (NACCHO) expressed concern that the recommendation states that the 

recommended age range is 16 through 18, but it can be given at 16 through 23 years of age. It 

was not clear to him how providers would interpret that. Short-term protection was also 

confusing to him, because that implied that there was a short-term period of time when he 

should choose to vaccinate. While the goal seemed to be to make people aware that coverage 

would not last that long, he did not think of that as being part of the recommendation. He 

agreed that making it a Category B would make it very difficult for a provider to interpret the 

information. 

Dr. Riley said that as the parent of one college-aged child and one child who just finished 

college, she was completely unclear about what the WG expected parents to do. If she or her 

daughter goes to the doctor and indicates that they have heard there is a vaccine that will 

protect her daughter from a deadly disease, they would have to rely on the doctor to make a 

value-based judgment about whether she should receive this vaccine. This kicks it back to the 

19-year-old who is going to call her mother, who is just as confused. 

Dr. Baker (Physician) said that as a WG member since 2003, Ms. MacNeil made one of the 

best presentations of the data she had ever heard. The data are frustrating. The vaccine is 

known to be protective short-term for at least 2 years, but that does not mean protection will not 

last for 5 to 10 years. This is a deadly disease, the cost-effectiveness analysis is terrible, but 

there are licensed and available vaccines. She agreed with Dr. Riley that an individual 

practitioner may have some difficulty in knowing all of the innuendos to counsel her or one of 

her daughters, but the vaccine will be available and will be paid for in an equitable manner. 

However, unlike huge health maintenance organizations (HMOs), it has been her experience 

with permissive recommendations in the past that smaller practices may not even carry 

Category B vaccines in their offices. While practitioners can council patients, the patients may 

have to go elsewhere to be vaccinated. Individuals should be allowed to have these vaccines 

paid for, either by their private health insurance company or by the VFC. 

Dr. Temte emphasized that as they have shown fairly recently, ACIP can make rapid changes 

in the recommendations based on emerging information. 

Dr. Harrison thought there was potential for inequity with a Category B recommendation, which 

could occur in terms of how knowledgeable a practitioner is about meningococcal disease. 

Dr. Campos-Outcalt thought a Category B recommendation was acknowledgment of the fact 

that in the future, with more vaccines against rarer diseases, they would not be able to 

recommend every vaccine for every person every time. There will have to be intermediate 

recommendations, and he thought Category B would fill that need. The vaccine is available. 

People can get it. They want to make it equitable, but they were not convinced at this point that 

every person should receive it. If the only option was a Category A recommendation, he would 

be forced to vote against this vaccine based on the data. Putting this into perspective, if even 

half of the cohort is vaccinated at the predicted cost, this would mean adding $2 billion to the 

VFC budget. CDC’s entire budget is $7 billion. There are 20,000 to 30,000 deaths a year in 

this country from mental health-related diseases in the same age category. The entire budget 

for SAMHSA is $3.6 billion. Adding a Category A recommendation would exceed SAMHSA’s 

entire budget. The world is bigger than just vaccines and vaccine-preventable diseases. To 

him, a Category B was a good option at this time. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Kimberlin (AAP) added that as he understood it, a Category B vote would encumber the 

dollars from VFC, assuming a VFC vote was approved. Assuming the numbers were correct, 

that would be $2 billion from the VFC funds. He did not think a Category B recommendation 

would keep that from occurring. He thought sometimes it was better to do nothing and wait for 

a while. 

Dr. Belongia did see a benefit in a Category B recommendation because it acknowledged the 

fact that ACIP does not have all of the answers at this point. Important questions remain that 

need to be addressed. However, usage will certainly increase due to a recommendation and 

that would allow for collection of additional observational data to further assess the safety and 

the impact of the vaccine in the population. While even one death due to serogroup B is too 

many deaths, they have to acknowledge that they have a responsibility also to ensure that they 

do not make recommendations that ultimately might be shown to have unanticipated harmful 

effects. 

Dr. Rubin thought that a Category B would be appropriate because fundamentally, it would 

send the message that there is a balance between the benefits and risks of the vaccine that 

each decision-maker should take into account. 

Dr. Hahn (CSTE) pointed out that with a Category A recommendation, many states will 

mandate the vaccine for school entry. Many states currently have kindergarten entry and 

seventh-grade requirements. With the lack of data, it would be a challenge to mandate the 

vaccine for school entry and could promote some backlash. 

Dr. Middleman (SAHM) voiced the Society for Adolescent Health and Medicine’s (SAHM’s) 

support for a Category B recommendation. 

Dr. Dwelle (ASTHO) expressed concern about the potential autoimmune factors. The incidence 

of thyroiditis in the US ranges from 12.1 to 24 per 100,000. Calculating that back to the 3,100 

reported, a maximum of up to .74 would be expected. There is a question about the safety of 

the vaccine as well. 

Ms. Stinchfield (NAPNAP) acknowledged the importance of the use of the vaccines for outbreak 

management and that local public health and colleges have to be prepared in advance to use 

the vaccine. Education of clinicians, adolescents, and parents about the signs and symptoms 

of meningococcal disease and early recognition, early treatment, and prompt community 

response may be one of the most important efforts they could make with regard to this disease. 

Dr. Romero emphasized that it is the responsibility of physicians to educate themselves on the 

risks and benefits of vaccines. Physicians must understand the risk of the disease and make 

recommendations as appropriate for the child. If there is a vaccine that works, it should be 

ACIP’s job to educate their colleagues and promote its use if a Category B recommendation is 

made. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

PUBLIC COMMENTS 

Dr. Temte reminded everyone that approximately 40 letters were received regarding this topic, 

and that all ACIP members were provided with copies of the letters. The letters were from 

universities, colleges, Chancellors of large systems, student health, and public health 

departments, student-government organizations. The National Meningitis Association (NMA) 

provided a document with over 1000 signatures, and Meningitis Angels provided a petition with 

601 signatures. Due to lack of time, Dr. Temte was unable to read all of the letters into the 

official meeting minutes but indicated that they would be included as part of the minutes. The 

letters are appended at the end of this document. 

Dr. Steven Black 

Pediatric Infectious Disease Specialist and Vaccinologist 

Thank you for the opportunity to speak. My name is Steve Black, and I've been a Pediatric 

Infectious Disease Specialist and Vaccinologist for more than 30 years. I guess I want to make 

two disclosures. I'm a consultant for GSK, Protein Sciences, Takeda, and WHO. And 

secondly, I really hate this disease. I've seen many children and adolescents who have died or 

whose lives have been ruined by meningococcal B disease, children and adolescents who are 

completely healthy and had the potential for a long and happy, productive life. This disease 

changed my life also. I was a third-year pediatric medical student, and my first rotation was 

pediatrics. One of the first patients I saw was a girl named Laurie who had meningococcal 

sepsis and was admitted to the ward. On the third day of the hospitalization, the resident I was 

working with was walking to another hospital to take a call and didn't show up and was found 

dead on the sidewalk subsequently of meningococcal B disease. I think, prior to that time, I 

was planning on being an echocardiographer. Actually, the first paper I ever published was a 

cardiology paper. But this disease really changed my life and made me want to go into 

infectious diseases. It's now more than 40 years later, and we now have the possibility of 

prevention of this disease. Since meningococcal B disease is rare as we've heard, we're told 

that perhaps it's not cost-effective to prevent the hundreds of cases that still occur in this 

country. I think the people that say that, as was said by others, are considering these cases as 

numbers and not people. They're not seeing them as people and their families. They're not 

seeing the suffering associated with this disease and, really, the misery due to complications as 

well—not just deaths—in terms of amputations, blindness, et cetera that occurs. So costeffectiveness really, as has been said, and the GRADE criteria provided should not be 

considered alone as a criteria here for making decisions. Additionally, cost-effectiveness 

analyses that are performed prior to implementation really have not had a great historically 

predictive value. I was before this committee when the pneumococcal conjugate vaccine was 

considered. At that time, the cost per QALY was $85,000 or $90,000 per quality-adjusted lifeyear. There were several people on the committee who said that this was really not a costeffective prevention. As we know now, after vaccine introduction, this is now one of the more 

cost-effective vaccines that we have. So, I became a doctor to save lives, and I think that it’s 

difficult to save lives one on one, especially with meningococcal B disease, where it evolves so 

rapidly. And sort of one of the greatest fears of pediatricians and parents is to miss a case of 

this disease because, once it commences, the risk of sequelae and mortality is so high. So, I 

think the committee has an opportunity today to prevent these deaths, to prevent the suffering 

and loss of life potential in dozens of children each year, and I would urge the committee 

members to seize that opportunity and to routinely recommend this vaccine for children. Thank 

you. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Frankie Milley 

Mother of Ryan Milley

Founder / National Director, Meningitis Angels 

Hi my name is Frankie Milley. I’m the mother of Ryan and the Founder and National Director of 

Meningitis Angels. Monday, 17 years ago, I carried my only child into an emergency room, 

screaming, “He has meningitis.” Within two hours, there was blood coming from every orifice of 

his body, and I watched him die a horrible death. The last words Ryan heard were from his 

dad. “Daddy loves you, baby boy.” The last words Ryan said were, “I know.” I will never be the 

parent at a college graduation. I will never dance with my son at his wedding. I will never hold 

a grandchild, and I won’t have the care of a child in my old age. The stats that you have are not 

necessarily correct, and we know that because all the cases don’t get reported because it costs 

money, and some hospitals and some health departments don’t want to spend that money or 

don’t have it to spend for those reports. We know that kids are misdiagnosed when they come 

into the emergency room or they’re given antibiotics and once that antibiotic hits the 

bloodstream, it’s no longer diagnosable. Ryan’s cause of death was Waterhouse–Friderichsen 

syndrome (WFS). On the fifth day amended lab report, it was Group C meningococcal. I’ve 

been coming to these ACIP meetings for 12 years. I’ve testified at almost all of them, almost 36 

times. For a total of 108 minutes, I’ve been allowed to speak about my son and the importance 

of immunizing kids. In those 12 years, the working groups, the ACIP voting committee, and us 

old warriors that are here every time have come very far. We’ve left here celebrating, and 

we’ve left here crying. One of the worst was when we had a vaccine to prevent meningococcal 

B in infants and we didn’t get a recommendation for it. We still have parents calling us every 

day who have infants and children, “Why can't we get our kids vaccinated? Why are our kids 

dying? Why is my child so mutilated? Why couldn't I get that vaccine?” We know that 

permissive recommendations don’t allow for education of the disease and the vaccine. We 

know, in many cases, there’s no affordability or accessibility. We know that there’s a hesitancy 

of physicians and healthcare providers to give it because it’s really not recommended or it’s 

permissive. We know that there is provider reimbursement problems with a permissive 

recommendation. One thing this does is it really confuses parents about: Is my child fully 

protected or are they not fully protected? One of my parents right here in Georgia sent her 17­

year-old who is about to go to college this fall to her pediatrician to get her meningococcal B 

vaccine. Guess what? They gave her the conjugate again, the second one she’s had in two 

years, because they don’t know. They are not educated. There’s no real information out there. 

We are still seeing outbreaks in Oregon and the gay community. We’re seeing outbreaks on 

college campuses. We’re seeing random cases of adolescents. We still see toddlers and 

infants die with this disease or be left terribly mutilated. Again, I want to remind you, this, to me, 

is like having a ship that’s sinking. You have 100 passengers, 100 life vests, and you only give 

out 50, and the other 50 people on that boat drown as they watch their life vest hanging in the 

closet. How many tears do we have to cry and how many children and young adults have to be 

debilitated or die before we make this and we do the right thing and just stop this disease? I 

want to remind each and every one of you that look at stats, I know you have to do that, but 

each one of those stats, each one of those cases represent somebody’s child, somebody’s life. 

It represents a child or young adult who has lost limbs, faces, are blind or deaf, and live a really 

hard life. They represent parents who have gone through a divorce and financial and social 

ruin in their lives. Some of them watch their kids every day who suffer from seizures and all 

kinds of problems and never know if the next day their child is going to wake up or not. This is 

the life that I live with all of our families. Each one of those numbers that you talk about 

represent somebody’s child. Just remember that. So you know, permissive recommendation— 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

I’m disappointed. You know, I would like to think it’s a real step forward. But unfortunately, I 

think it's going to cause a lot more confusion in our world and among parents and physicians 

and payers. Thank you to the committee for your dedication and your hard work. I know that 

you don’t have an easy job. I know you’re all parents and grandparents. Dr. Temte, I especially 

wanted to say to you, you've been an amazing leader, and thank you for your care and your 

kindness and consideration of all of us. 

Scott Parkhurst 

Father of Jacob Parkhurst 

Thank you for letting me speak. Hi. My name is Scott Parkhurst. I’m from Portland, Oregon. 

My youngest of two sons, Jacob, was a 17-year-old junior in high school. Jake was an A 

student and was a member of the high school swim team. He also enjoyed snowboarding, 

golfing, and riding motor cycles. He was my mini-me. Jake would have graduated high school 

a few weeks ago. But, that was all taken away from him last year. It tears me up seeing his 

classmates enjoying graduation and getting ready to head off to college. This should have 

been one of Jake’s shining moments. Fifteen months ago, on a Sunday afternoon, Jacob said 

he didn’t feel well. By Monday morning, he was in the emergency room. The ER doctor pulled 

Jake’s mom and I aside and informed us that Jake may not survive and appeared to have 

bacterial meningitis. I told Jake to fight for his life and he yelled back to me, “Okay” as he was 

taken off to intensive care and put into a medically induced coma. That was the last contact I 

ever had with Jake. On Tuesday morning, the doctors ran an EEG to check his brain activity. 

At that point, they determined he was brain dead. In 36 hours, my son was dead. Cause of 

death: bacterial meningococcal, serogroup B. Every day, almost every hour, I have thoughts of 

Jake. A lot of times it hurts real bad, especially when I hear of another person becoming sick 

with meningitis. I end up reliving the final tragic moments of Jake’s life. This has affected 

everyone in my family. We have had to deal with depression, marriage counseling, alcohol, 

drug use, and rehab, to name a few. It completely turns your world upside down. My oldest 

son, Jeff, was heading to OSU in September and planned to live in a dorm. We were all 

terrified of him possibly contracting meningitis. Thanks to Alicia Stillman and her interview on 

the Today Show, I followed her lead and took Jeff to Canada to get the serogroup B 

vaccination. We shouldn’t have to take our children to other countries to get vaccines. The 

most recent outbreak at U of O has hit home, as this is my home state and I have lots of friends 

and family that have children attending U of O. Fortunately, they have all been vaccinated. But 

at this time, only half the student body has been vaccinated, and it’s been over five months. 

The permissive recommendation doesn’t cut it. It creates an inequality and just creates a lot of 

confusion, and I just don’t feel that’s effective. I understand this disease only affects a small 

percentage of the population. But when it’s your son, daughter, grandchild, cousin, niece, or 

friend, it’s 100%. I don’t think anyone here who has children would want to lose their child to 

something that is preventable. I strongly encourage the panel to make a routine 

recommendation and stop the spread of this deadly, debilitating disease. Jake didn’t get that 

chance. Thank you. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Alicia Stillman 

Mother of Emily Stillman 

Founder / Director, Emily Stillman Foundation 

I am Alicia Stillman, and I thank you very much for giving me the opportunity to speak here 

today. I’m here as Emily Stillman’s mother, and I’m also here as the founder and the director of 

the Emily Stillman Foundation. This is my Emily. She’s 19 years old forever. She’s beautiful, 

she’s talented, she’s smart, and she was a 19-year-old college sophomore. Emily was not a 

part of an outbreak. She was a one, and all she had was a headache. She called me one 

night, “I have a headache.” I said, “Why do you think you have a headache? I bet you’re 

coming down with the flu.” She said, “No, mom, I was up all night studying for two big tests. 

But don’t worry. I did good.” I said, “Great, so take a couple of MOTRIN® and we’ll see how 

you feel in the morning.” The morning never came. By the time I was called back to the 

hospital the next day and told to get en route immediately, Emily was in a coma. I never saw 

the gorgeous eyes open. I never saw her look at me, tell me she loved me ever again. My 

favorite thing about Emily was when she would hug, she would hug with her whole body. It 

wasn’t like limp arms around you. And now, when I want a hug, it’s a cold stone. This is what I 

hug when 

I hug my daughter now. Emily happened to have been my daughter, but she could have been 

any of your daughters. She could have been any of your grandchildren. She could be your 

next-door neighbor. She wasn’t a number. She was a person with a future, a wonderful future 

ahead of her. Last weekend, Emily would have graduated from college. So, instead of being 

here today listening to “B, A, permissive, not permissive, are we going to let kids get protected, 

are we going to let parents protect their families” I should be moving my daughter to a new city 

to start her life. Would she be starting grad school? Would she be on the stage? Would she 

be starting a new job? 

Instead, I am begging you to protect our kids. To give parents the ability to vaccinate their 

children with a vaccine that wasn’t protecting my daughter. I made my daughter a promise 

when I said goodbye to her. I promised her I would be her voice. I promised her, “I don’t know 

how this could happen. You were protected. I did everything I was told to do, but I will figure 

out how this could happen and I will make sure it doesn’t happen to other people.” When I 

formed the Emily Stillman Foundation, that was my mission and that’s what I did. And yes, 

before our FDA approved those vaccines, I schlepped busloads to Canada and I protected 

whole families in Canada with this vaccine. Now we have it here and I field phone calls and 

emails all day long from parents all over the country who can’t get their hands on this vaccine. 

Their doctors say they don’t even know that there’s one approved. They don’t even know it’s 

approved. That’s what they tell them. “Oh, but don’t worry. Your kid doesn’t need it.” So with 

a permissive vaccine, who will pay for it? Who will carry it? I worry about that. I worry that in 

2015 we’re going to become communities of have and have-nots and knowledge and 

knowledge-nots. And that’s not okay. I have letters here that I know you’ve all seen, in my 

folder, from every university in the State of Michigan: University of Michigan, Michigan State, 

Kalamazoo College, Wayne State School of Medicine, Central, Northern, Eastern, Western. I 

know you’ve all seen them. They all want their campuses protected. Emily isn’t a number. A 

one doesn’t matter. When it’s your child, a one might as well be a million. And I’ll close just by 

telling you that, in Judaism, we are taught, “To save one life is like saving the whole world.” 

And you are taxed with that. You are taxed with that today, so please save the one and save 

the world. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Mike Barnes 

Father of Jimmy Barnes 

National Meningitis Association 

My name is Mike Barnes, and I am here today as a representative of the National Meningitis 

Association. I’m joined by my wife, Charlene, and my daughter, Kendall. We lost our 20-yearold son, Jimmy, to serogroup B meningococcal disease this March. He went to the ER on a 

Monday with a terrible headache, neck pain, and high fever. He was told it was the flu and sent 

home. He was gone in 28 hours. He was not a college student living in a dorm, and his story 

was not covered by the media, so I’m here to share it with you today. He was, however, we 

thought, fully vaccinated, including with the meningitis vaccine. Charlene and I were not able to 

have our own kids. It took many years, but eventually, we were able to adopt Jimmy when he 

was three days old. Five years later, we adopted our daughter, Kendall. We had the perfect 

family. We had a great life. Jimmy was a great kid. He was always joking and smiling. 

Everyone liked him. He had a million friends. As a parent, it seems as if childhood lasts 

forever, but those teenage years fly by. First he’s struggling with homework. Next, he’s 

learning to drive and applying to college. Jimmy chose Colorado State University to be near 

skiing, but he found the work load overwhelming and decided to return home to New Jersey. 

We were glad to have him back. Shortly after his return, our family moved to Florida. He loved 

the beach life, and he made a million friends just like he always had. Jimmy and Kendall were 

always very close. They were so protective of each other. They loved each other very much. 

They were more than brother and sister. They were good friends. Kendall will feel this loss for 

the rest of her life. There are now so many things I don’t have to worry about anymore, like 

when he’s coming home at night or what kind of job he’ll get or if he’s getting enough sleep. I 

don’t know what kind of man he would've turned out to be. I won’t be able to bounce his kids on 

my knee or take them to the beach. I can never hug him or tell him I love him ever again. 

Jimmy made our world a brighter place. His light is out, and we wonder if the world will ever be 

as bright again. In my family, among my two children, the incidence of men B was 50%. For 

Jimmy, it was 100%. Today you have ability to make sure no other parent has to stand here 

and share a story of how their son or daughter died. On behalf of my son, Jimmy, who is no 

longer here, I implore you to extend the current vaccine recommendations for adolescents to 

include a vaccine to prevent meningitis B. Thank you. 

Theresa Wrangham 

National Vaccine Information Center 

Dr. Temte indicated that an effort had been made to permit a letter to be read into the record by 

telephone, but after a discussion with the Management Analysis and Services Office (MASO), 

the decision was made for Dr. Temte to read the letter for the record. He apologized to anyone 

who found this to be unfair, but explained that it was an intermediate step. 

“Thank you for the opportunity to provide public comment today. Founded in 1982, the 

nonprofit National Vaccine Information Center advocates for the institution of vaccine safety and 

informed consent protections and public health policy and laws. We support the availability of 

all preventive healthcare options, including vaccines, and the right of consumers to make 

educated, voluntary healthcare choices. Meningococcal disease is devastating to those 

stricken, and the public has the right to use MenB vaccines. As the committee considers 

routinely recommending MenB vaccines, please consider the following information. The current 

US population is estimated to be over 321 million. According to CDC, meningococcal disease 

in the US ranges from 800 to 1200 cases annually. One-third of these cases are serogroup B, 

with 60% serogroup B cases occurring in children too young to benefit from the MenB vaccines. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The CDC also has acknowledged that humans are the only natural reservoir for N. meningitidis. 

As children grow into adulthood, the vast majority have bactericidal antibodies against this 

disease. Accordingly, a CDC report published in 2000 revealed that routine recommendation of 

meningococcal vaccines for college freshmen living in dormitories was not cost-effective. The 

report stated that it would take 300,000 to 500,000 doses of vaccine annually to prevent 15 to 

30 cases of disease and one to three deaths. The costs were $600,000 to $1.8 million to 

prevent one case of disease and $7 million to $20 million to prevent one death. Although this 

report precedes licensure of MenB vaccines, MenB vaccine cost-effectiveness findings would 

be similar. Because ACIP’s routine recommendation often translates into legal vaccine 

mandates in many states, choice in recommendation versus vaccine requirements were 

unifying themes noted in CDC’s 2011 stakeholder report by meningococcal vaccines. We have 

listened with deep sympathy to the experiences shared by parents whose children and family 

have been devastated by invasive meningococcal disease. During ACIP meetings and the 

CDC’s 2011 public engagement on meningococcal vaccines, some parents and their healthcare 

providers did not make themselves aware of meningococcal vaccine availability. These parents 

have a right to know about the benefits and risks and availability of meningococcal vaccines so 

they can make an informed decision for their children. However, with regard to ACIP 

recommending that all children get MenB vaccines, the data is clear that a universal-use 

recommendation is not justified. It would have far-reaching consequences that will be costly 

and unnecessarily burdensome to parents, adults, and government agencies. NVIC 

respectfully requests ACIP to vote against MenB vaccine universal-use recommendation. We 

encourage ACIP and the CDC to revisit stakeholder report and need for greater flexibility in the 

ACIP recommendations. 

Laurie Stelzer 

Mother of Sara Stelzer 

National Meningitis Association 

Hi. My name is Laurie Stelzer. I’m a representative for the National Meningitis Association. In 

October 2014, I lost my smart, funny, confident, and very healthy 18-year-old daughter, Sara, to 

serogroup B meningococcal disease. She called us from her school in San Diego, California 

complaining of flu-like symptoms. The next morning, her severe headache prompted her to go 

to the ER. We got there in three hours, but she was already in the ICU on a ventilator and in a 

coma. By that evening, they thought she was brain dead. She died from serogroup B 

meningococcal disease just a few days later. Sara donated her organs to save the lives of 

others. Sara loved to laugh and sing. Even though she only sang in the car, she surprised us 

and auditioned to sing at her high school graduation. She chose the song “I’ll Stand By You” 

and brought a stadium of people to their feet. She was just beginning her life, and we expected 

a great future for her. Serogroup B meningococcal disease stole that from her. No mother 

should have to bury a child. It’s just not the right order of things. If one fewer child dies of this 

preventable disease, that would be a very strong legacy for Sara. I took her for all her 

recommended vaccines. We got everything they told us to do. At that time, serogroup B 

vaccines were not available. They were not approved, but they are now. It would be 

devastating for one other child to lose their life, knowing that it could be avoided. You have the 

opportunity to prevent other families from going through what we went through. The available 

vaccines to protect against serogroup B meningococcal disease must be recommended broadly 

for all adolescents, just as the ACWY vaccines have been. This disease destroys families and 

lives. Protecting our children against all strains of this life-shattering disease is really the right 

thing to do. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Jacquelynn Ross

Sister of Stephanie Ross 

National Meningitis Association 

I just want to thank you for the opportunity to let me speak today. My name is Jackie Ross and 

I’m the sister of Stephanie Ross, the Drexel University student who died from meningitis B in 

March of 2014. My sister was awesome, smart, funny, and compassionate. But I’m here 

representing the National Meningitis Association. I’m here to do what I can to prevent the kinds 

of losses that so many of us have had to endure. My parents spoke to you in October. On 

behalf of my parents and also on behalf of all of Stephanie’s and my own college classmates 

who want to be protected from the devastating effects of all the meningococcal strains, I’m 

asking you to, please, make a broad vaccination recommendation. Since December, my 

parents have worked to get me the serogroup B vaccine. This was no easy task. It took many 

phone calls and e-mails between them, the vaccine manufacturers, my pediatrician, various 

pharmacies, and even the Department of Public Health. I was finally able to get vaccinated just 

last week, but the process took nearly six months and it only occurred because our pediatrician 

finally thought to recommend that we look into a travel vaccination clinic. My parents also tried 

to get the vaccine through several pharmacies. Most did not have the access to it, and those 

that could get it did not have anyone on staff that could administer it, so ordering it would not 

have mattered. Parents should not have to work this hard to get an FDA-approved vaccine to 

protect their children. When you’ve lost a family member, you go the extra mile to do what it 

takes to protect your family. My fear is that a lot of people will feel uncomfortable not getting the 

vaccine through their doctor or that there will not be enough outlets for everyone to get 

vaccinated. Without a broad recommendation from you today, doctors won’t recommend that 

young adults be vaccinated against this deadly threat. That would be a terrible thing that would 

sadly only be reversed after more people like my sister suffer the devastating effects of 

serogroup B meningitis. In the span of a few hours, I lost my only sister, my mentor, and my 

best friend. I don’t want that to happen to anyone else. 

Sister of Andrea 

National Meningitis Association 

I am here because my sister passed away nine months ago. My sister’s name was Andrea. 

She was one of those kids who excelled at everything. From a very young age, she won 

awards as school, played sports, and still somehow managed to have a social life. Like most 

college-bound kids, her first question when she got into Georgetown’s pre-med program was, 

“How am I going to afford this?” It turns out she didn’t have to worry about it because she was 

awarded the Gates Millennial Scholarship, but Georgetown actually offered her a full ride. So, 

she had a lot of potential and she would have been an amazing doctor. In September of her 

Sophomore year, after a few days of feeling sick and being misdiagnosed as having a viral 

infection, she was found in her dorm room in a coma and unresponsive. The next day my sister 

passed away from serogroup B meningococcal disease. She was 19. Seeing my sister in a 

coma was one of the most traumatic experiences I’ve ever had. I remember begging her to 

wake up. I stayed with her until they finally took her off life support until the end. The only way I 

know how to describe losing her is like trying to breathe with just one lung. I struggle every 

single day. It’s been nine months, and I still struggle to move forward with my life and so do my 

parents. I’m so glad there’s a vaccine now, but it won’t save lives unless it’s used. As a college 

student who was not aware of this disease, I just assumed my sister and I were protected. I 

know that, unless a doctor specifically recommends a vaccine, college students are unlikely to 

get it or know to ask about it. It was Andrea’s dream to help people as a doctor, and making 

sure that other people get vaccinated would mean she did just that. Please make sure no one 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

else has to go through the heartbreak our family has gone through and provide a broad 

recommendation for this vaccine. It’s the right thing to do. Thank you. 

Lynn Bozof 

Mother of Evan Bozof 

President, National Meningitis Association 

I’m Lynn Bozof, President of National Meningitis Association. Many of you had heard me talk 

about losing my son, Evan, to meningococcal disease 17 years ago and it doesn’t get any 

easier. About a month ago, my younger son, Ryan, who is a physician in Atlanta, called on his 

way to the ER with a 104.5 fever and the worst headache imaginable. You all know what I 

thought. Ryan is fine, but for a few hours, all I could think of was, “I can't go through this again. 

I can’t lose another child to meningococcal disease.” It was a horrible déjà vu. Meningococcal 

disease has scarred my life forever. Seventeen years ago, I didn’t know the devastation that 

this disease could wreak, but I know now. In my role with the National Meningitis Association, I 

see and I hear it daily. You’ve already heard from a number of advocates who know it all too 

well, from siblings who have not only lost their best friend, but have lost part of their parents 

who are going to be forever grieving the loss of a child; from parents who bravely soldier on and 

share their stories so that this doesn’t happen to any other family; and from survivors who bear 

their physical and emotional scars with grace and dignity. A handful of our adolescent survivors 

have submitted written testimony and it’s in your packets, and there are copies on the back 

table for everyone to see. About two weeks ago, NMA issued an open letter and invited people 

who had been affected by meningococcal disease or who were interested in broad MenB 

recommendations to sign an open letter. As of this morning, we have almost 1240 signatures 

from all 50 states. It’s been an overwhelming response. We have gotten so many touching, 

heartbreaking comments from MenB families I didn’t know existed. We’ve captured about 20 of 

them. They are in your packets. There’s also a link if you want to read all of them, and there 

will be copies on the back table. You have the power to prevent other families from going 

through this. We can protect our children. We need to protect our children. It’s the right thing 

to do. Thank you. 

Andy Marso

Meningitis Survivor 

Thanks. So my name is Andy Marso. I’m a meningitis survivor. I’m here on my own time, and 

my own dime, and I have no conflicts. Last time I was here, I was wearing a suit, but honestly, 

it’s really hard for me to tie a tie anymore. Plus, I thought it was kind of important that all of you 

see what my arms look like now, because they didn’t always look like this. So, you all 

remember last year when there was this really awful infectious disease going around and all 

kinds of people were really clamoring for a vaccine? Remember Ebola? Well, what I found 

interesting about the Ebola scare is that meningococcal B infections are far more prevalent in 

the United States. They are more contagious. They have a similar fatality rate in the US. 

Generally speaking, they kill people more quickly than Ebola does. So, based on the general 

US public’s reaction to Ebola, I think it’s pretty safe to say that if all Americans understood the 

gravity of meningococcal B infections, there would be even more people backing me up here as 

I urge all of you to adopt a broad vaccination recommendation—a Category A recommendation. 

Unfortunately, most people don’t know how afraid of this disease they should be. I know 

because 11 years ago, I went from a perfectly healthy college student to almost dead within 24 

hours. Then I spent four months in the hospital having my skin debrided and parts of my limbs 

amputated. As I told you all a few months ago, the first year of my medical bills were almost $2 

million. That’s just for the initial year. $2 million. That would’ve bought a lot of vaccines, right? 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

And that doesn’t even account for the year of work that my parents missed and that I missed as 

I was recovering, nor for the ongoing medical costs that I’ve had every year since. I’ve been 

fortunate to have health insurance, but I’ve basically maxed out my out-of-pocket every single 

year and I probably will for most of my life. I’ve accepted that. Again, I know there’s concerns 

about the cost of these vaccines, but I hope you’re accounting for all of the costs of not 

vaccinating and you’re also accounting for the cost burden and who bears the cost burden. Is it 

society at large, or is it just families like mine? 

To this point, we’ve gotten off the hook for a lot of medical expenses due to meningococcal B 

infections because 15% of those who get them die quickly, which saves us money. But as 

critical care continues to improve, how many of those will survive, but survive with costly, 

lifelong injuries like mine? We also know that every year more and more Americans move from 

rural areas into cities. Isn’t it logical that we’ll see more outbreaks of this disease as more 

people cluster together in population centers? We’re already seeing an outbreak right now in 

Chicago, for instance. A meningococcal B vaccine for college campuses has already proven 

ineffective. As we saw at the University of Oregon, it takes weeks or months to ramp up a mass 

vaccination campaign. If you wait until a second or third case before you start, you’re just 

inviting unnecessary deaths in the interim. In Oregon, it was the fourth case that proved fatal. 

Meanwhile, you have an entirely different recommendation for the quadrivalent vaccines, which 

is confusing and frankly paints you into a bit of a corner. These new vaccines prevent the same 

disease with the same horrible effects as the quadrivalent. The data shows they’re safe and 

effective. If you hand down lesser recommendations for these new vaccines, we will know that 

it’s strictly for economic reasons so that the government and the insurance companies can save 

a few dollars. But will the government or insurance companies compensate families who lose 

unvaccinated loved ones to this disease? Will they compensate families like mine? How would 

that change the economic equation if they were forced to? 

As we’ve heard, England now has meningococcal B vaccines in its national health program, 

meaning any British citizen can walk into any doctor’s office and get the shot without paying a 

dime out-of-pocket. They found a way to afford that. Why can’t we? By the way, their 

government negotiated with the drug companies for a price of 20 British pounds per shot. 

Unless I’m doing the currency exchange way wrong, that’s a lot less than $400 American. So 

with all due respect, I think your cost-effectiveness study is bunk and you should pretty much 

just disregard it. If you hide behind that as a reason for lack of a recommendation, I think that’s 

going to be pretty cowardly. Are you going to set up another situation like we had when we 

were waiting on FDA approval in which Americans are second-class citizens globally when it 

comes to preventative healthcare? Americans used to lead the world on scientific issues. 

When JFK said, “We're going to send a man to the moon by the end of the decade,” he didn’t 

then say, "But only if it’s cost-effective.” When Jonas Salk was developing the polio vaccine, I 

don’t think he ever said, "Gee, I sure hope the cost of this shot is offset by what it saves in 

medical costs. Otherwise, this will all be for naught.” No. They said, “We’re going to send a 

man to the moon. We’re going to wipe out polio” and they did it. They inspired an entire 

generation of scientists. I don’t hear a whole lot of that boldness from this panel today. What I 

hear is a lot of fear and a lot of hedging. I hear a lot of doctors who seem to want people to be 

vaccinated, but don’t want to take the responsibility for being the one to tell them to get 

vaccinated. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

I need your help. Since I’ve survived meningitis, part of my purpose in life has been to make 

sure others don’t get it. So I have spoken to as many school groups as will have me, and I’ve 

testified in several different state legislatures. I wrote a book. Every time I hear about another 

person getting ill with this disease, it strikes me right in my chest. What if I had done more? 

What if I had talked to more people? Maybe my warnings would have reached that person. 

Maybe that person would have gotten vaccinated or not shared that bacteria-ridden cup or 

recognized the symptoms and gone to the hospital in time. Surviving this disease gave me a 

terrible responsibility to talk about it almost every day for the last 11 years. To relive the panic, 

the debridements, skin grafts, the amputations, the emotion anguish of watching my body 

disintegrate at age 22. You can help me with this responsibility. You can put this vaccine in 

every health insurance plan and every pediatrician’s office in America. Please, don’t let me 

down. I believe this is why I went through that pain. I went through all of that so that I could be 

here today in front of you pleading for you to help me make sure others don’t go through it. 

Please, don’t let me down. 

Dr. Leah Luckeroth 

Andy Marso’s Initial Physician 

That’s a hard act to follow. Greetings from Kansas. I’m Dr. Leah Luckeroth. I am here 

speaking on my own behalf as a mother, friend, and a physician. I have absolutely no conflicts. 

Eleven years ago, Andy Marso presented to Watkins Health Services at the University of 

Kansas carried in by two of his friends due to extreme pain in his extremities. I was getting 

ready to leave the building for lunch when I received a call from one of our nurses concerned 

about a student who had just arrived. I walked into the treatment clinic and knew immediately 

that this was an emergency when I saw the dusky, cyanotic color of Andy’s skin. I placed my 

hand on his forearm, seeing for the first time the rash of meningococcemia. It was more 

frightening than the pictures I had seen in textbooks. Andy, who was a National Merit Scholar 

and on track to graduate number one in his class in the School of Journalism in May, was still 

coherent and answered my questions as I asked the nurse to call 911. In less than 10 minutes, 

the ambulance had arrived. One physician was talking to Andy’s friend Clay about close 

contacts, another physician was talking to Andy’s father in Minnesota, and I had reviewed his 

case with the Infectious Disease Specialist at our local hospital. Time was of the essence. This 

deadly disease strikes without warning. I can remember taking my dose of Cipro and trembling 

as I felt that Andy would not survive the night. I hugged my two daughters closely that evening, 

realizing with a jolt of reality that this student could’ve easily been my child. Over the ensuing 

hours and days, there would be meetings at Andy’s scholarship hall where he lived, with the 

campus newspaper students that he worked with on a daily basis, his soccer buddies, and an email would be sent campus-wide from the Chancellor. The university would later adopt a policy 

mandating the meningococcal ACYW vaccine for all students living on campus. Andy lost most 

of his fingers and part of his feet, but stands tall today as a miracle and advocate for the 

prevention of meningitis. He continues to educate medical professionals and the public about 

the disease. Now that more people than ever have viable health insurance that puts prevention 

first, we have the opportunity to save lives with a simple vaccine. This past week, my daughter 

received her first dose of the meningitis B vaccine before she travels to college in August. 

Eleven years later, I felt that jolt of reality knowing how fortunate my daughter was to have this 

option that did not exist for Andy. Please do the right thing and approve this vaccination for 

prevention of meningitis in all adolescents and college students and everyone else. There is no 

dollar amount that could ever replace Andy or any student. Prevention and education are the 

key factors to lowering the cost of healthcare. I agree with what Andy said. I don’t have a 

business degree, but if it only costs $50 in Europe and it costs $400 here, certainly we can get 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

an MBA to help us with the price. I am thankful to be here today as an advocate for meningitis 

B prevention and as part of Andy’s amazing life story. Thank you. 

Mara Berger 

Mother of Adam Berger 

Mara Berger from Chicago, Illinois. I don’t have any affiliation yet, but I’m a grieving mother. In 

2005 the FDA licensed and approved the conjugate Menactra® for routine use in 9 months to 

55-year-olds. The FDA said after thorough research that the vaccine is effective, safe, and 

immunogenic. However, at that time, your predecessors of the ACIP committee didn’t 

recommend the vaccine for the FDA’s approval. Instead, the ACIP prioritized and gave the 

vaccine approval and recommendation for adolescents only. To date, there is still no 

recommendation for 9-month-olds to 55-year-olds. Now the CDC does take care of the children 

and young adults and adolescents, but what about the adults 21 to 55 who die or get maimed 

from this insidious disease? The Strain C with sepsis, Neisseria meningitis C and septicemia. 

CDC does not recommend the vaccine to healthy adults in their literature. My son, Adam, was 

a beautiful human being. I took him into an emergency room thinking he had the flu. I’ve read 

this so many times on the Internet. Emergency room doctors must be retrained and the nurses. 

They know nothing about meningococcal disease. Everything they do, they only focus on the 

flu. We went in the morning. He had a 1040 fever. They told us it was the flu. We went home, 

and when we returned, he had the most virulent headache. The triage nurse told us to go 

home, that it was flu, and there was nothing they could do. I threw a big stink. They were mad 

at me because I wouldn’t stop saying, “We’re staying. I don’t care what you say. We’re 

staying.” They made my son wait five hours in the emergency room where he could have 

infected everyone because he was so contagious. When he was finally seen, they gave him 

the antibiotic because he had septicemia. Now I did not know—I had heard of meningitis, but I 

really did not know anything about meningococcal disease. Well, I studied it and researched it. 

I would challenge any infectious disease doctor here on my knowledge versus theirs. 

I can’t believe that for 10 years this vaccine has been approved by the FDA and the ACIP 

committee has not recommended the vaccine. Do you think that healthy adults don’t get this 

disease? It’s the healthy people that get the disease, because they don’t have enough 

antibodies to protect them, plus he was a nursing student at a prestigious private hospital. He 

thought he got the recommended vaccines. Come to find out, after his death, he didn’t get a 

meningitis vaccine because the private hospital follows the CDC’s recommendations that only 

epidemiologists should get the vaccine. Aren’t hospitals full of bacteria? Sick patients come in 

with meningococcal disease. Do you know how many firemen, emergency staff, paramedics 

have gotten the disease from a patient they’ve transported to hospitals? I believe that adults 21 

to 55 are at most risk. A friend of mine, she’s 50 years old, she went to her doctor. She said, 

“Do I need a meningitis vaccine?” “Oh, no. You don’t live in a dorm.” That’s the mindset of 

many doctors. Since the vaccine is not recommended for adults, doctors don’t keep up on the 

information about meningococcal disease. They talk foolish. I can go into Walgreens right now 

and get Menactra® shot. I don’t have to ask anybody. As long as the FDA approved it and 

licensed it, we really don’t need your recommendation. The only way we need your 

recommendation is so that the insurance companies pay for the vaccine. I’m lucky. I have Blue 

Cross/Blue Shield and they pay for the vaccine whether you recommend it or not. But in the 

meantime, people are dying. The ACIP committee has an obligation to stop the disease at any 

cost. Controlling outbreaks is not eradication. The only eradication is vaccine. You have to 

educate the public from preschool to grad school—the parents, the children, the nursing staff, 

the colleges. Anyone should be able to get this vaccine, even staff at schools. Recommend it 

routinely the way the FDA intended 10 years ago. There have been thousands of maimings 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

and deaths, and you’ve turned a blind eye. I don’t get it. I implore you that the ACIP and the 

CDC have to come together and approve this Menactra® for the ACWY-135 as soon as 

possible. This disease is not rare. It’s sporadic. All over the country. One here. Two there. 

Please act accordingly and responsibly. Thank you. 

Dr. Deborah Wexler 

Executive Director 

Immunization Action Coalition 

I’m Dr. Deborah Wexler, Executive Director of the Immunization Action Coalition (IAC). IAC is 

proud to receive funding from CDC, almost all vaccine companies, individuals, coalitions, and 

more. I’m here today because I have attended ACIP meetings for more than 15 years and have 

witnessed hours of discussion as the committee strives to determine the right thing to do in 

protecting the health of the nation. It is within this context that I offer the following reasons for 

you to support a routine recommendation for MenB vaccine. First, for simplicity and clarity. 

ACIP has recommended the use of meningococcal vaccine against Serotypes ACWY for 10 

years. How can we justify doing less for serogroup B? In addition, having a routine 

recommendation for one meningococcal vaccine and a permissive recommendation for the 

other is unnecessarily confusing for both parents and providers. Parents may erroneously think 

that their vaccinated children are protected from Meningitis when in reality, they have been 

vaccinated against only ACWY. A routine recommendation for MenB would be simpler to follow 

and would alleviate confusion for everyone concerned. Second, it was my understanding that 

insurance is unlikely to pay for a vaccine which lacks a routine ACIP recommendation, which 

would create a two-tiered approach to disease prevention. I’ve learned here today that, 

perhaps, VFC would cover this vaccine if it were a permissive recommendation. But, it still 

concerns me that private insurance and HMOs may not cover the vaccine because it’s a 

permissive recommendation. If it’s not on the CDC immunization schedule, the vaccine may 

not even be discussed unless a knowledgeable parent brings it up. Third is cost, and the 

people here who have spoken before me have been so eloquent on this topic. Ironically, cost is 

a consideration both in support of and in opposition to a routine recommendation. ACIP tends 

to focus on the high cost of the vaccine per case prevented. But, what about the cost to a 

parent whose child has died from a preventable disease? And what is the cost to a young adult 

of having one or more limbs amputated or having other lifelong disabilities from a preventable 

disease? And what are the costs, both in dollars and the emotional toll, for colleges and 

communities dealing with an outbreak of a preventable disease? These concepts must also be 

factored into any discussion of cost. As public health professionals, we are all dedicated to 

prevention. I know that you as ACIP members are charged with making recommendations that 

balance difficult and seemingly competing objectives. But to me, the answer is clear. I choose 

prevention, and I ask you to choose a routine recommendation to protect all teens with MenB 

vaccine. You have the power to prevent a deadly and devastating disease that can have an 

overwhelming impact on young people and all the people who love them, as we have just 

heard. A routine recommendation is quite simply the right thing to do. Thank you. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Kamay Lafalaise

National Consumers League 

First, I’d like to take a moment to share my deepest respects and condolences for the families 

and the survivors that have shared their stories with us today. So, thank you. Good morning, 

everyone. My name is Kamay Lafalaise, representing the National Consumers League (NCL), 

and I have no conflicts of interest to declare. Based in Washington DC, the National 

Consumers League is the nation’s oldest consumer advocacy organization, founded in 1899, 

and provides the consumer perspective on matters that affect consumers, including healthrelated issues. In February, the National Consumers League Executive Director, Sally 

Greenberg, stood before this committee urging it to add serogroup B meningococcal, or MenB, 

vaccines to the routine schedule of vaccines. We are here today to echo that same message 

before more lives are needlessly lost to this devastating disease. Making safe and effective 

medications and healthcare widely available to all Americans has been a long-standing priority 

to NCL. We recently conducted a survey of parents to explore attitudes, behaviors, and 

misconceptions regarding vaccines. Among other things, we found five significant points that I’ll 

share with you today. First, the majority of adults, 87%, support mandatory vaccinations for 

school-aged children. Second, 81% of parents find healthcare providers to be a trusted source 

of vaccine information. Third, about 30% of parents still believe that vaccinations can cause 

autism, which demonstrates the critical need to educate the public and strengthen our 

message. Fourth, 84% of parents cite protecting a child from disease as the top reason to 

vaccinate, followed by protecting family from disease, helping to eliminate the disease, and 

lastly, protecting the community from disease. Fifth and finally, of all childhood diseases, 

parents are most concerned about meningitis. Not only do these findings highlight that there is 

an ongoing need for vaccine education, but that Americans see vaccines as a way to protect 

our children and community from disease, and they take very seriously the threat of meningitis. 

A routine or Category A recommendation for the MenB vaccines would allow for patient 

education about the disease, and the availability of this new vaccine before an outbreak occurs. 

Because of the highly contagious nature of the disease and its debilitating effects, including loss 

of limbs and death, the vaccine to prevent MenB would be available to all parents and children, 

not just those who are aware of the vaccine and specifically request it or those who can pay 

out-of-pocket costs. You have heard powerful testimony today from several people afflicted by 

this frightening disease. If we wait, it could be too late. How many lives need to be lost before 

we take preventative action? We see no reason to expose anyone to this terrible illness when 

complete protection and prevention is available. Once again, NCL believes that parents and 

young people should have access to these two FDA-approved vaccinations before a deadly 

outbreak occurs and, therefore, both vaccines should be added to the routine schedule. Thank 

you very much. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Neal Raisman 

Father of Isaac Raisman 

Spokesperson, Global Healthy Living Foundation 

Good morning. My name is Neal Raisman. In 2005, I was the father of two. Today, I am the 

father of one. On the morning of September 27th, my youngest, my son Isaac, woke with a 

headache and was dead of meningitis by 4:30 the same day. I found his body. He had died 

less than 12 hours from the time he had told us he had a headache until he died. A vaccine 

would have prevented his death. It’s an epidemiological story you all know too well, but it’s a 

personal story I never wanted to know. Today, I’m here as a spokesperson for the Global 

Healthy Living Foundation. Together we’re asking this committee to endorse the FDA labeling 

recommendation for broad immunization to prevent the invasive disease, death, and physical 

devastation caused by meningitis serogroup B, especially for individuals 10 through 25 years of 

age. My appearance here today in your committee meeting could not come at a more 

immediate time. Lauren Jones at the University of Oregon added her name to the list of those 

who have died of meningitis. A UC Davis student was also diagnosed in February, and others 

in Tennessee, Washington DC, and Rhode Island. These schools now see the need for a 

vaccine to be available to all of their students, not just the ones who can afford it. Since the 

FDA approved the vaccine for meningitis strain B in November 2014, there have been over 50 

cases of meningitis strain B. Did they get infected because the ACIP didn’t act to make the 

vaccine available to all? Perhaps. Although the vaccine was available to those who could 

afford to pay for it, without your recommendation, as you know, insurance companies and 

Medicaid won’t cover the costs. It’s not difficult to conclude that informed people with the 

money to pay for the vaccine have lived and those who can’t afford it or don’t even know about 

it have been infected. This is counter to everything the ACIP, the CDC, the FDA, and the NIH 

stand for. Your endorsement vote for the FDA recommendation would realign this committee 

with its mission, with the values and expectations of parents with college-aged children. We 

expect the government to tell us when the health of our children is in danger, and then help us 

decide what to do. Because meningitis is nearly always fatal or at least physically devastating, 

the low number of people affected masks the toll these cases take on families such as mine and 

on communities. My job today is to help you understand the depth of the emptiness we parents 

feel every day and the heartache we feel for those parents who are about to join our ranks—the 

ranks of families minus one. Please act so other young people and their families are not so 

violently affected by meningitis. Let there not be another Lauren Jones or an Isaac Raisman, 

my son who died of meningococcal. You can do this, and I urge you to do so today. As for 

cost-benefit analysis, what is the cost of a life and what is the benefit of an early death? 

Dr. Temte thanked all of the public commenters for sharing what must be very difficult stories, 

and expressed ACIP’s appreciation for their heartfelt and very thoughtful comments. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Proposed Recommendation 

Jessica MacNeil, MPH 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Ms. MacNeil showed and read through the WG’s proposed recommendation language for use 

of MenB vaccines in adolescents: 

“A serogroup B meningococcal (MenB) vaccine series may be administered to 

adolescents and young adults 16 through 23 years of age to provide short term 

protection against most strains of serogroup B meningococcal disease. The preferred 

age for MenB vaccination is 16 through 18 years of age. (Category B)” 

In addition, the following language would be provided as guidance for use: 

 MenB should be administered as either a 2-dose series of MenB-4C or a 3-dose series 

of MenB-FHbp 

 The same vaccine product should be used for all doses 

 Based on available data and expert opinion, MenB-4C and MenB-FHbp may be 

administered concomitantly with other vaccines indicated for this age, but at a different 

anatomic site, if feasible 

 No product preference to be stated 

Discussion Points 

Dr. Temte asked whether this would appear on the schedule or whether the WG had 

considered this. 

Ms. MacNeil indicated that this had not been discussed specifically, but she thought the WG 

would be open to having a line in the schedule for the vaccine, with footnotes to explain it 

further. 

Dr. Vazquez said that to be clear, as a pediatrician who attends clinics, there is a difference in 

having a vaccine on the schedule versus on the table. It is very important for practitioners trying 

to figure out how to counsel their patients and parents that there is agreement. If the vote is for 

a Category B recommendation, she thought that the MenB vaccines should appear on the table 

and not solely in the footnotes. 

Ms. MacNeil said that they could work with the Childhood Schedule WG to put that on the 

schedule for next year. 

Dr. Romero added that as the Chair of the Childhood Schedule WG, he will make sure that they 

have very strong discussions about including these on the schedules—on the table, not just as 

a footnote. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Loehr (AAFP) pointed out that the schedules have certain colors, none of which match this 

recommendation. The current colors are for “recommended for all children,” “catch-up 

immunization,” or “certain high-risk groups.” A new color would be needed for this 

recommendation. 

Dr. Schuchat reminded everyone that there have been other options over the years, and the 

schedule is voted on every year. In 2009, there was an equivalent of a Category B for HPV 

vaccine for boys in the period before there were additional data on the outcomes, at which time 

it became a Category A. It was on the schedule with a hatched-mark, not a footnote. The 

schedule committee will look at that option for this year’s schedule, and that will come back to 

the full ACIP in October 2015 for vote. 

Dr. Reingold had two different immunization schedules, one of which went through age 18 and 

the other which started at age 19. He presumed this would have to appear on both. 

Ms. MacNeil confirmed that it would. 

Given the uncertainty regarding duration of protection, Dr. Harrison wondered why “short-term” 

protection was specified. 

Ms. MacNeil replied that the WG’s rationale for adding that language was to ensure that people 

are aware that prevention may not be long-term and that these vaccines will not prevent all 

cases. 

Dr. Belongia thanked all of the survivors and family members for sharing their stories. He said 

that his hesitation at the moment regarding the Category A, which he could easily endorse, 

pertained to safety concerns, not cost-effectiveness. He wondered if it would be helpful to add 

some language to the recommendation indicating that the committee will reevaluate the 

potential to make a Category A recommendation when additional safety and effectiveness data 

become available. 

Dr. Temte reminded everyone that for the Tdap recommendation for pregnancy, ACIP specified 

that the safety aspects would be paramount to that recommendation and requested that 

ongoing safety studies be performed. 

Dr. Harriman emphasized that the vaccine would be covered under the VFC program, and that 

insurance companies would be compelled to pay with a Category B recommendation. 

Dr. Netoskie (AHIP) commented that AHIP values vaccines and recognizes that they offer great 

value. Many health plans are already covering this vaccine. AHIP also wants to ensure that as 

determinations are made through ACIP, it is important to understand ACIP’s view of vaccine 

effectiveness, cost, and safety. Health plans will cover A and B recommendations when 

provided in-network. Also, grandfathered plans would be exempt from this mandate. There are 

also post-approval timelines following publication in MMWR. There would be some varied 

uptake with plans over the course of the following year. Uptake in physicians’ offices would 

probably also vary depending up their views of the vaccine. He would say that health plans 

tend to be more proactive regarding promotion of Category A recommendations based on 

appropriate age, risk, et cetera. Vaccines with Category B recommendations, permissive, are 

somewhat difficult to promote broadly in the plans, whether promoting to clinicians or patients 

who may have gaps in care based on appropriate age or vaccine need. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Kempe emphasized that it is extremely important to collect data about safety, efficacy, and 

carriage. This is clearly important to incorporate into guidelines. 

Dr. Bennett thought they could feel confident this would occur. This is similar to the 

recommendation for pneumococcal vaccine in those over the age of 65. There are a number of 

studies going forward to try to address the effectiveness of that recommendation, and she 

thought this was the same type of situation. While she did not believe they actually 

incorporated that into the recommendation, there was discussion. 

Ms. Pellegrini stressed that members considering support of a Category B recommendation 

were not doing so because they were wildly enthusiastic that it would be exactly the right 

recommendation long-term for this vaccine. There simply was not adequate information at this 

point to support a Category A recommendation. In that context, she urged the manufacturers to 

provide those data as quickly as possible. She also encouraged CDC to determine how to 

increase reporting to better understand the burden—not just the numbers of cases and the 

numbers of deaths. It is important to understand the long-term consequences and the cost of 

medical expenses to survivors and families out-of-pocket. Survivors are dealing with profound 

lifelong consequences, which should be factored in. If a Category B recommendation was 

made, she thought this offered a golden opportunity for CDC to study the policy impacts with 

regard to whether providers carry the vaccine and how patients take it up. This could provide 

an incredibly useful case study for the future and for understanding the impact of the 

recommendation ACIP makes. She looked forward to the vote during this session, as well as 

revisiting it in the near future. 

With all due respect, Dr. Reingold submitted that this is one of the diseases for which the 

burden of disease is known as meningitis is one of the better reported diseases in the US. The 

ABCs data are very compelling and are extrapolatable to the rest of the country. He does think 

more effectiveness and safety data are needed. 

Dr. Even (ACHA) reiterated that ACHA understands the devastating burden of the disease. 

They are highly committed to education about vaccines in general, as well as the booster dose 

that is needed for the quadrivalent meningitis vaccine. They are pleased to have reached a 

point of making some recommendations, which offers a springboard before the fall semester. 

Vote: Use of Serogroup B Meningococcal
 

Vaccines (MenB) in Adolescents and Young Adults
 

Dr. Campos-Outcalt made a motion to accept the wording as stated for the use of serogroup B 

vaccines in adolescents and young adults. Dr. Rubin seconded the motion. The motion carried 

with 14 affirmative votes, 1 negative vote, and 0 abstentions. The disposition of the vote was as 

follows: 

14 Favored: Bennett, Belongia, Bocchini, Campos-Outcalt, Harriman, Karron, Kempe, 

Pellegrini, Romero, Reingold, Riley, Rubin, Temte, and Vazquez
 

0 Abstained: N/A
 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Vaccines for Children 

Dr. Jeanne M. Santoli 

Immunization Services Division 

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention 

Dr. Santoli indicated that the purpose of this revision was to update the resolution to allow 

individual clinical decision-making regarding the use of serogroup B Meningococcal vaccines in 

children aged 16 through 18 years. She reminded everyone that this resolution had two parts. 

The first regarded meningococcal conjugate vaccines, while the second pertained to serogroup 

B meningococcal vaccines. There were no proposed changes to the Meningococcal Conjugate 

Vaccine section of the resolution. For the section regarding serogroup B Meningococcal 

vaccines, the proposed changes are underlined: 

Eligible Groups 

 Children aged 10 through 18 years at increased risk for meningococcal disease 

attributable to serogroup B, including:
 

 Children who have persistent complement component deficiencies (including 

inherited or chronic deficiencies in C3, C5-C9, properdin, factor H, or factor D or 

taking eculizumab [Soliris®]) 

 Children who have anatomic or functional asplenia, including sickle cell disease 

 Children identified to be at increased risk because of a meningococcal disease 

outbreak attributable to serogroup B 

 Children aged 16 through18 years without high risk conditions may also be vaccinated 

In the section on recommended schedule and intervals, the table was updated to remove 

specific information that indicated this is for high-risk use and a correction was added in the 

footnote. There were no changes to the recommended dosing schedule: 

No changes were made to contraindications and precautions, which can be found in the 

package inserts available at: 

http://www.fda.gov/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM093833 

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 0 Opposed: N/A
 

 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

No changes were proposed to the statement regarding updates based on published 

documents: 

[If an ACIP recommendation regarding meningococcal vaccination is published within 12 

months following this resolution, the relevant language above (except in the eligible 

groups sections) will be replaced with the language in the recommendation and 

incorporated by reference to the publication URL]. 

Vote: VFC Resolution for Use of Serogroup B
 

Meningococcal Vaccines (MenB) in Adolescents and Young Adults
 

Dr. Romero made a motion to approve the VFC MenB vaccines recommendation for 

adolescents and young adults. Dr. Bocchini seconded the motion. The motion carried with 15 

affirmative votes, 0 negative votes, and 0 abstentions. The disposition of the vote was as 

follows: 

15 Favored: Bennett, Belongia, Bocchini, Campos-Outcalt, Harriman, Harrison, Karron, 

Kempe, Pellegrini, Romero, Reingold, Riley, Rubin, Temte, and Vazquez
 

0 Abstained: N/A
 

General Recommendations 

Introduction 

Dr. Marietta Vázquez

Chair, General Recommendations Work Group 

Dr. Vázquez reminded everyone that the General Recommendations document is published in 

the Morbidity and Mortality Weekly Report (MMWR) every 3 to 5 years, and addresses a broad 

range of clinical practice issues that are relevant to all vaccines as opposed to the vaccinespecific publications. The General Recommendations are intended to address topics that 

cannot be attributed to a single vaccine, but that are germane to the practice of immunization in 

general. A number of topics have been or are being revised, including the following: 

 Timing and Spacing of Immunobiologics 

 Contraindications and Precautions 

 Preventing and Managing Adverse Reactions 

 Reporting Adverse Events After Vaccination 

 Vaccine Administration 

 Storage and Handling of Immunobiologics 

 Altered Immunocompetence 

 Special Situations 

 Vaccination Records 

 Vaccination Programs 

 Vaccine Information Sources 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

During this session, a vote was planned for the second half of the document to include the 

following topics: 

 Altered immunocompetence 

 Special situations 

 Vaccination records 

 Vaccination programs 

 Vaccine information sources 

Content already reviewed and discussed by ACIP include: 

 Altered immunocompetence (June 25, 2014) 

 Special situations (February 20, 2013) 

 Vaccination records (October 23, 2013) 

 Vaccination programs (June 25, 2014) 

 Vaccine information sources (October 29, 2014) 

A vote is necessary for CDC clearance and publication. The presentations during this session 

pertained to changes that have occurred since ACIP last discussed the document; special 

situations, including updates related to ACIP vaccine-specific statements; and major revisions in 

three sections: Altered Immunocompetence, Vaccination Records, and Vaccination Programs. 

Dr. Raymond Strikas presented on behalf of Dr. Andrew Kroger who was unable to attend. 

Dr. Vázquez thanked ACIP for the opportunity to serve over the last four years; Dr. Kroger, the 

CDC lead, who is one of the most organized and detailed-oriented persons she has ever had 

the pleasure to work with; and the WG in general. 

General Recommendations: Final Five Sections 

Raymond Strikas, MD, MPH, Medical Officer

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Strikas thanked ACIP for the opportunity to present revisions to the General 

Recommendations on Immunization, and Dr. Andrew Kroger for leading the Working Group with 

Dr. Vazquez. He indicated that ACIP members had drafts in front of them in both track changes 

copies and clean copies. He frequently referred to page numbers and line numbers in this 

presentation, and these numbers corresponded to the track changes version of the document. 

Regarding the Altered Immunocompetence section, many of the changes were already 

presented to ACIP in June 2014 for which Dr. Strikas shared background information. The 

2011 General Recommendations currently contains a section on Altered Immunocompetence. 

The source for revised content to this section comes from the cleared ACIP MMWR vaccinespecific statements, and the Infectious Diseases Society of America’s (IDSA’s) position 

statement on this topic. The full citation for the IDSA document, on which ACIP member Lorry 

Rubin is first author, is as follows: 

Rubin, LG, Levin MJ, Ljungman P., et. Al. 2013 IDSA Clinical Practice Guidelines for
 

Vaccination of the Immunocompromised Host. Clin. Infect. Dis. 2014; 58: e-44-100.
 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

This is an evidence-based set of guidelines that involved multiple stakeholders in its 

development. Prior to publication, CDC was asked to comment on potential areas that might 

represent a deviation from the ACIP vaccine-specific statements. The IDSA’s publication, 

entitled Clinical Practice Guideline for Vaccination of the Immunocompromised Host, expands 

greatly upon the content in the 2011 General Recommendations on Immunization, which is why 

the General Recommendation’s WG incorporated as much as possible into the revised General 

Recommendations and the vaccine-specific statements. There are some minor areas of 

difference between this document and the vaccine-specific statements. The major goal of the 

WG has been to distinguish those topics which are “General” in nature, and to stay away from 

vaccine-specific recommendations because of the risk that they might not match ACIP 

statements exactly. However, there are relatively few such differences. 

The revisions to the Altered Immunocompetence section include four major topic revisions and 

source material. First, the IDSA identified some new conditions and some new medications 

under the classification of altered immunocompetence, so these were added to the General 

Recommendations. Second, those who were present during the June 2015 meeting may recall 

that a major change in the tenor of discussion was the added weight given to the issue of 

vaccine effectiveness. This is described in detail in the IDSA document, and is an issue that 

applies to both live and inactivated vaccines. It involves the complex issue of potentially 

withholding a vaccine if the condition or the medication is present, and if the vaccine is withheld, 

at what interval it is considered safe and effective to give the vaccine after the altered 

immunocompetence is no longer present. Third, the General Recommendations have been 

updated to discuss altered immunocompetence as an indication to vaccinate outside of the 

routinely recommended ages, and relies exclusively on CDC vaccine-specific statements. 

Fourth, the discussion of vaccination following hematopoietic cell transplants (HCT) has been 

updated, using evidence from the IDSA document primarily, but also relying on some CDC 

vaccine-specific statements as well. 

Here are some of the new additions to the list of conditions and medications that are described 

in the General Recommendations: 

 Conditions 

 Interferon gamma/interleukin 12 axis deficiency 

 Interferon alpha deficiency 

 Interferon gamma deficiency 

 Phagocyte function disorders (e.g., Chediak-Higashi syndrome) 

 Medications 

 Induction/consolidation chemotherapy 

 Anti-B cell antibodies (example rituximab) 

 Combination Medication/Conditions 

 Patients with major antibody deficiencies receiving immunoglobulins 

These are specific categories defined in the IDSA guidelines, and have relevance because of 

changes to the current general recommendations. This section contains language that allows 

physician discretion in the determination of whether any of these conditions are present. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Some of the new recommendations relevant to these conditions reflect categories of vaccines 

that can either be administered or withheld. In most cases, this information is presented in a 

table on Page 13 of the marked up version. Certain conditions require only the withholding of 

live bacterial vaccines, not live viral vaccines. This includes interferon gamma/interleukin 12 

axis deficiencies. But there are also recommendations to withhold both live viral and bacterial 

vaccines in patients with interferon alpha deficiency and interferon gamma deficiency. Teasing 

out the different pathways of these interferons will be the job the of the immunologist or other 

specialty physicians, which is why it is critical that providers using the General 

Recommendations be provided with opt out language for referral to these specialists. For other 

conditions, the General Recommendations borrow some of the specific rationale for withholding 

of live vaccines. For instance, patients with leukocyte adhesion defects, myeloperoxidase 

deficiency, and Chediak-Higashi syndrome have specific deficits in T-cells and natural killer 

cells that render a reduced immune response to live viral and live bacterial vaccines, which is 

why both categories of live vaccines are to be withheld for such patients. For other phagocyte 

deficiency disorders, such as chronic granulomatous disease, these cell lines are not deficient 

so withholding is restricted to live bacterial vaccines. 

IDSA also invoked some of these conditions in the context not only concerns with safety and 

effectiveness of live vaccines, but also the effectiveness of inactivated vaccines. Conditions in 

which IDSA supports withholding both categories of vaccines include induction/consolidation 

chemotherapy (Table Footnote, Page 15) and patients with major antibody deficiencies 

receiving immunoglobulins (Table Footnote, Page 15). IDSA also defines a category of 

conditions as “high-level immunosuppression” including cancer chemotherapy (P5, L6), 

radiation therapy (P5, L6), solid organ transplantation (P11, L13), human immunodeficiency 

virus (HIV) with immunosuppressive parameters defined (P6, L22), patients receiving high-dose 

immunosuppressive corticosteroid therapy (P10, L33), and patients receiving biologic immune 

modulators (P11, L36). The page and line numbers represent the location in the General 

Recommendations where these medications are described. 

Incorporating IDSA recommendations occurred against a backdrop of what is currently 

described in the 2011 General Recommendations. The General Recommendations already 

had an extensive discussion of intervals. In terms of the specific intervals that are proposed 

based on integrating General Recommendations with IDSA recommendations, for those types 

of conditions/medications labeled “high-level immunosuppression,” IDSA harmonized with 2011 

General Recommendations in recommending a 3-month interval from medication to vaccine, at 

least with respect to cancer chemotherapy and inferred high-level steroid use as well (P5, L10). 

There is a vaccine-specific exception of a 1-month interval between certain categories of highlevel immunosuppression, notably zoster vaccine, in which a 1-month interval has been 

established by ACIP vaccine-specific statement. These intervals vary by direction: when a live 

vaccine is given first, IDSA recommends a 1-month interval from the live vaccine to the 

medicine or condition, and for inactivated vaccines there is a 1-month preference but a 2-weeks 

recommendation from inactivated vaccine to medicine (P5, L8). IDSA has introduced 

exceptions to the 3-month rule when medicine is given first. For Anti-B cell antibody therapy, 

the interval should be 6 months (P5, L15). For solid organ transplant rejection therapy, the 

evidence supports a range of 2 to 6 months for an interval, which practically could be 

considered a 2-month interval (P11, L32). IDSA also defines a category of immunosuppression 

defined as “low-level immunosuppression.” Examples are lower doses of corticosteroids; 

alternate day corticosteroids; and the examples set out in the ACIP zoster-statement with 

defined doses of azathioprine, methotrexate, and 6-mercaptopurine. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The discussion of intervals and withholding vaccines is woven into the text of the new draft with 

General Principles (Beginning P4, L44). Live vaccines effectiveness concerns and safety 

concerns are both relevant, with primacy given to safety. With inactivated vaccines there are 

safety concerns and effectiveness concerns, with effectiveness being the primary rationale for 

withholding. Inactivated influenza vaccine is an exception to the withholding rule, but the dose 

should be repeated if given when the patient is no longer immunocompromised (Table, P15). 

The topic of altered immunocompetence as an indication to give a vaccine outside of routinely 

recommended ages (P2, L13) is less complex because it involves simply updating the General 

Recommendations with content from vaccine-specific statements. The changes are highlighted 

on Page 2 beginning with Line 13, and apply primarily to the bacterial vaccines Hib, 

meningococcal conjugate vaccine, and pneumococcal vaccines. These recommendations are 

primarily driven by rare conditions like asplenia and complement component deficiency. The 

meningococcal vaccine languages requires modification here to be consistent with ACIP’s prior 

recommendations. 

Patients who have received an HCT (hematopoietic cell transplant, bone marrow transplant, or 

umbilical cord stem cell transplant) require special consideration because not only do they have 

altered immunocompetence, but also their treatment wipes out their entire immune system, 

also called immunoablation. This treatment removes immune cell memory. Therefore, these 

patients eventually require revaccination with a complete or near complete primary series of all 

vaccines received previous to the transplant. Specific regimens were described in the journal 

Biology of Blood and Marrow Transplant in 2009 [Tomblyn M, Chiller T, Einsele H, Guidelines 

for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: 

A Global Perspective Biol Blood Marrow Transplant 15: 1143-1238 (2009) 2009 American 

Society for Blood and Marrow Transplantation]. The 2011 General Recommendations 

borrowed content from this journal and cited it heavily in the General Recommendations. CDC 

also placed the article on its website for reference. Reliance on this source document was 

vetted through ACIP during the presentations that led up to the 2011 iteration of the General 

Recommendations. The IDSA provides detailed recommendations for vaccination of HCT 

recipients in their 2013 document, and the lead author of the 2009 blood marrow paper is an 

author on the IDSA document as well. 

Revaccination with the following vaccines is recommended post-hematopoietic cell transplant: 

DTaP, PCV13, PPSV23, Hib, HepA, HepB, meningococcal vaccines, IPV, IIV, HPV, Varicella, 

and MMR. Revaccination is not recommended with BCG, LAIV, typhoid vaccine, rotavirus 

vaccine, and zoster vaccine. The interval following the HCT and beginning the revaccination 

series varies depending upon whether the vaccine is inactivated or live. The interval for 

inactivated vaccines is 3 to 6 months. Most are 6 months, though pneumococcal vaccine is 

specified as 3 months. For live vaccines, the interval is 24 months and the responsible 

physician should be sure the patient is immunocompetent and does not have chronic graft 

versus host disease. The guidance in the IDSA recommendations address revaccination doses 

following HCT. However, there is little discussion about first-time vaccination following HCT; 

that is, administration of doses that have not been given before the hematopoietic cell 

transplant. CDC does have specific guidance for some vaccines. Some of this guidance is 

unpublished such as for zoster vaccine, Tdap vaccine, and Hib vaccine. For zoster vaccine, 

IDSA says vaccination is not recommended because the vaccine that should be administered is 

varicella vaccine post- HCT, presuming that VZV immunity is ablated. Unpublished CDC 

guidance for zoster vaccine is that it can be administered following risk-benefit analysis. There 

is the possibility that someone post- HCT will be exposed to varicella disease and then become 

a candidate for zoster vaccine. Personal communications with pertussis subject matter experts 

(SMEs) at CDC state that if pertussis-containing vaccination is not documented prior to the 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

transplant, then post- HCT vaccination recommendations should consist of routine vaccination 

based on age. Finally, revaccination with three doses of Hib vaccine are recommended by 

CDC regardless of Hib vaccination prior to hematopoietic cell transplant. This is in the Hibspecific ACIP statement. 

Some sections from the draft are unchanged from the 2011 General Recommendations. One 

of the most important is that the level of immunocompetence should be determined by a 

physician. The General Recommendations identifies certain categories and laboratory tests, 

but this is not meant to be all-inclusive. There is a section on Vaccination of Household 

Contacts of Immunosuppressed Persons. Some language was added on the length of time for 

rotavirus vaccine virus shedding. Clarification was added regarding the definition of a 

“protected environment” with respect to health-care providers to determine whether they should 

preferentially receive IIV as opposed to LAIV. Otherwise, the language in this section provides 

a strong recommendation to vaccinate household contacts of persons with altered 

immunocompetence, and this language is harmonious with that in the IDSA document. 

The major changes to the Special Situations section of the General Recommendations, none of 

which is new since the content was presented to ACIP in February 2013, is language stating an 

exception to vaccination of breastfeeding women. Breastfeeding is considered a precaution for 

Yellow Fever (YF) vaccine since there have been cases of apparent vaccine-derived disease in 

breastfeeding infants who were not vaccinated themselves but whose mothers were (P6, L 33). 

Also, the Vaccination in Pregnancy section is now harmonized with Tdap ACIP vaccine-specific 

recommendations (P7, L 29). The language from the 2011 document was kept regarding a 

physician’s decision to vaccinate by the intramuscular (IM) route for patients with bleeding 

disorders. They can choose to do this if the bleeding risk is acceptable. 

Changes to the General Recommendations in the section on Vaccination Records were 

presented to the ACIP in October of 2013. These changes describe the increasing capacity of 

vaccination registries, also known as Immunization Information Systems (IIS). As described in 

the draft, capabilities of an operational IIS are as follows (P2, L26): 

“A fully operational IIS also can prevent duplicate vaccinations, forecast when the next 

dose is due, limit missed appointments, allow recall for those who missed appointments, 

determine when vaccines need to be repeated (evaluation), reduce vaccine waste, and 

reduce staff time required to produce or locate vaccination records or certificates.” 

There also is a reference to Meaningful Use integration (P2, L36), defined as the capacity of an 

IIS to integrate its functionality with other electronic health records (EHRs). Language from 

CDC’s web site is placed into the General Recommendations: 

“Electronic health records should maintain interoperability with IIS’s as part of an effort 

to improve the quality of care, reduce health disparities, engage patients and families in 

their health, improve the security protection for personal health information 

(REFERENCE www.cdc.gov/ehrmeaningfuluse/introduction.html”). 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The Vaccination Programs section of the General Recommendations outlines programmatic 

aspects of immunization. New additions to this section of the document include the addition of 

language from the National Vaccine Adult Standards (P1, L6) stating: 

“All healthcare providers, whether they provide immunizations or not, should incorporate 

immunization needs assessment into every clinical encounter, strongly recommend 

needed vaccine(s) and either administer vaccine(s) or refer patients to a provider who 

can immunize, stay up-to-date on, and educate patients about vaccine 

recommendations, implement systems to incorporate vaccine assessment into routine 

clinical care, and understand how to access immunization information systems (i.e. 

immunization registries).” 

The Vaccination Programs section is divided into a discussion of child immunization, adolescent 

immunization, and adult immunization. No major revisions have been made to the section on 

child immunization or adolescent immunization. However, language has been included in the 

adult immunization section related to the Affordable Care Act (ACA). The language in the draft 

reads: 

“Effective for private health insurance plans drafted or updated after September 2010, 

coverage for ACIP recommended vaccines must be covered without deductibles or copays, when delivered by an in-network provider.” (P10, L7) 

Since the draft was developed, official language related to the ACA has been changed, so the 

internal CDC preference was to change the language to read: 

“The Affordable Care Act (ACA) requires insurance companies to cover all 

immunizations that are included on the immunization schedule with no copay and no 

deductible.” 

This new language emphasizes the role of the Child and Adult Schedules for defining 

immunization coverage. It also does not emphasize the fact that some insurance companies 

are grandfathered out. The new language does not emphasize “private” insurance companies, 

although Medicare is subject to additional regulation that might not be completely harmonized 

with ACA. 

In terms of Vaccination Information Sources, the following is a listing of organizations and 

projects related to immunization in the US: 

 CDC-INFO Contact Center 

 National Center for Immunization and Respiratory Diseases (NCIRD) 

 American Academy of Pediatrics (AAP) 

 American Academy of Family Physicians (AAFP) 

 American College of Physicians (ACP) (new) 

 American Congress of Obstetricians and Gynecologists (ACOG) (new) 

 Immunization Action Coalition (IAC) 

 Vaccine Education Center (VEC), at the Children’s Hospital of Philadelphia 

 Institute for Vaccine Safety (IVS) 

 Group on Immunization Education–Society for Teachers of Family Medicine (GIE-STFM) 

 State and Local Health Departments 

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A URL and short description of activities are listed for each of these groups. The National 

Network for Immunization Information was removed, which was formerly an affiliate of IDSA, 

AAP, AAFP, PIDS, American Nurses Association (ANA), National Association of Pediatric 

Nurse Practitioners, ACOG, University of Texas Medical Branch, Society for Adolescent 

Medicine, and the American Medical Association (AMA). The National Network for 

Immunization Information is currently under new direction, and it is unclear which organization 

is the parent organization. 

Discussion Points 

Dr. Temte indicated that members were missing a document, but had seen it prior to the 

February 2015 ACIP meeting and it was made available electronically as well. 

Dr. Kempe proposed a brief addition. Her group has conducted several surveys recently 

showing the knowledge about IISs, particularly among adult providers, is negligible. She 

wondered whether, under capabilities of operational IISs, there could simply be a statement 

made that all states have either regional or state IISs. 

Dr. Strikas indicated that this was fine with him, but pointed out that the committee should weigh 

in. 

With the mobility of the population, Dr. Dwelle (ASTHO) was concerned with the interstate and 

interoperability of IISs. He wondered whether that was discussed and if recommendations were 

made about this in the document. 

Dr. Strikas indicated that it is alluded to, but is not discussed in detail. 

Dr. Moore (AIM) thought the CDC recommendation to remove the reference to in-network 

providers and simplify the statement on coverage may prove to be more confusing than helpful 

to readers. From an operational standpoint in dealing with people looking for coverage for their 

vaccines, the fact that the coverage that is required is through in-network providers is critically 

important. Many local health departments are not yet in-network providers. When an uninsured 

person presents to a health department, they have to be charged for vaccines or be told to go 

elsewhere to receive them. She urged the inclusion of the in-network provider clause to prevent 

confusion. 

Referring to Slide 23, Dr. Strikas said that the rationale for inclusion of the second bullet was 

that it was simpler. If he understood the comment, Dr. Moore was favoring at least a mention of 

in-network providers and perhaps closer adherence to the ACA language. 

Dr. Moore (AIM) expressed a preference for the original language. Even though it is more 

detailed, it is more accurate. When reading it, there is so much confusion regarding what is and 

is not covered, the particular component about in-network providers for private insurers is a 

major issue operationally for immunization programs educating the public about where to obtain 

vaccines. 

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Ms. Pellegrini strongly agreed with Dr. Moore and expressed a preference for the original 

language with its greater level of detail and accuracy. She asked whether it would be 

appropriate to offer a motion at this state. Dr. Temte replied that it would. Ms. Pellegrini offered 

a motion to revert to the original language. Dr. Temte did not believe this rose to the need for a 

full motion and vote, but asked whether it would be acceptable to the WG to revert to the 

original language. This was acceptable to everyone. 

Regarding revaccination post-HCT, Dr. Bocchini pointed out that 24 months after stem cell 

transplant, YF vaccine could be administered. 

Dr. Strikas responded that if this is in the current recommendations, it can be addressed in the 

General Recommendations. 

Dr. Temte asked whether there was general agreement to make this addition without a motion 

and vote. This was acceptable to everyone. 

Dr. Bennett asked whether there were any data regarding how many states have adult IISs, and 

whether it is required. 

Dr. Kempe responded that they do not specifically have adult IISs, but the majority of states do 

have the ability to enter adult records. She did not know how many actually do enter adult 

records. 

Dr. Moore (AIM) added that CDC publishes data annually on the status of IISs. Her recollection 

was that over 40 states have lifelong registries in which adult records can be included. The 

point is well-taken that many adult providers do not realize this, but with Meaningful Use and 

forcing providers to send EHR information to IISs, the word is getting out that providers of 

immunizations can send their information to IISs in most states. The IISs need to be used 

much more effectively, and providers need to be aware of their capacity. The programs are 

committed to educating adult providers about the benefits. 

Dr. Hahn (CSTE) added that in many states, IIS use is only required for children but is available 

for use in adults. With the move for promoting IISs for adults, the data should become more 

robust over time. 

Dr. Temte commented that Wisconsin has a very functional registry that has a huge amount of 

population data for adults. He uses this on a daily basis and it is tied directly into their Epic 

EHR so that they do not have to go outside of the firewall to bring the data in. His mission has 

been to encourage people not to trust the data within Epic, but to always go to the IIS because 

the reliability is so good. There is a difference between a state registry being able to and 

actually doing so, so this is where a lot of emphasis should be placed on this. 

Ms. Hayes (ACNM) indicated that the ACNM has been trying to promote the IIS among 

midwives who are vaccinating their patients. They have found that the CDC website is 

outdated, though it is not really CDC’s fault. She was not sure that if they promoted the CDC 

site for IIS, it would offer the most current data. In many states, the public health departments 

have been so gutted financially, they do not communicate the current status. She suggested 

that if something was included in the General Recommendations, that it would guide clinicians 

to their own states rather than CDC’s list. 

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As a practicing physician, Dr. Fryhofer (AMA/ACP) shared something that occurred 

approximately a year ago. She was trying to determine the pneumococcal vaccination history 

for a patient. She wrote a prescription for Prevnar®, which the patient took to the pharmacy. It 

was not in the immunization registry. Nothing was ever faxed to her. She called the pharmacy, 

CVS, which did give the vaccine but said they are not the ones who put it in the immunization 

registry. It goes to a corporate office which does it. It took an hour to determine whether this 

patient had her pneumococcal vaccination. Perhaps the General Recommendations could 

contain a statement that pharmacists need to do this as well. 

Dr. Foster (APhA) suggested adding the APhA website to the list of immunization resources. 

Pharmacies are governed by pharmacy practice laws in each individual state; therefore, every 

state will be different in terms of what is required for the registry. If it is required in Georgia for 

example, that would be regulated by the State Board of Pharmacy. Corporate complications 

also occur. It is not possible to make a broad statement about how this is handled throughout 

the country. 

Dr. Kempe emphasized that her original point was that many providers do not even know about 

the existence of an IIS or what it is. At a minimum, she thought they should indicate that each 

state or region has an IIS and that each provider needs to be in touch with their state IIS. 

Information about how to do that should also be included. In Colorado, there is pretty 

sophisticated use of the adult side as well. CVS, Target, and other providers are submitting 

data to the system. But, this is highly variable. 

Dr. Temte asked whether any language needed to be added or changed with regard to this 

issue. 

Dr. Belongia suggested that a possible addition would be to state that, “Providers should be 

aware of state and/or regional IISs and requirements for reporting.” 

Dr. Strikas concurred with the suggested language and indicated that the most recent data 

could be cited about the number of states that have the capability to include adult data, and that 

providers should be aware of this. There is some language in the Adult Standards that could 

perhaps be included as well. 

Dr. Temte asked if this would be acceptable to everyone. This was acceptable to everyone. 

Dr. Bennett emphasized that there is a major difference between “availability” and 

“requirement.” She was curious regarding the CDC’s progress in working with health 

departments to make adult vaccine reporting a requirement. 

Dr. Schuchat indicated that strengthening the IISs has been a major priority, and CDC has been 

putting substantially more resources into this effort. An Intergovernmental Advisory Committee 

has been established to advise about CDC’s strategic plan and priorities. The resources 

allocated to states and other third party groups for IIS have been increased. A lot of innovative 

work is underway, such as with the pharmacy-registry interfaces. The requirements are statedriven, so CDC does not do this. However, the agency believes that making use easier is the 

best plan. Bidirectional flow is the direction of the field, and CDC has been extremely 

supportive in terms of large financial investments. 

Dr. Fryhofer (AMA/ACP) stressed that this is not about state requirements. This is about taking 

care of patients. This should be a very patient-centered statement that the right thing to do, 

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when so many different people are administering immunizations, is to enter the information into 

the IIS. If that is too hard, it should be given to a provider. Keeping the information in a little 

pharmacy and not sharing it with the world does not help patients or the bottom line. These are 

expensive vaccines and patients need them. 

Dr. Moore (AIM) expressed appreciation on behalf of the states for the additional funding being 

received to make the IISs more robust, and they are working very hard on this. She agreed that 

the focus should not be on requirements for use. For example, requirements are prohibited in 

Tennessee. Given the way the law was founded, providers cannot be required to report. 

Instead, the system is made as useful, useable, and valuable to the clinician in the provision of 

patient care so that they couldn’t imagine not using it. The problem is that they do not 

necessarily know about it and all of its wonderful benefits yet, but AIM is working on that and is 

adding an increasing number of clinicians each day whose data are being submitted from their 

EHRs. That does include pharmacies, and AIM is very grateful to the pharmacies that are 

submitting their information into the IIS. The immunization neighborhood works best when 

everyone knows what everyone else is doing. The IIS is the heart of that neighborhood where 

everyone has the ability to open the door and see what the patients have received. Any 

support for getting people engaged will be greatly appreciated regardless of the patient’s age. 

They recognize that adult providers really need to be brought on board, because with the 

expanding adult schedule, there is so much benefit for patient care in knowing what others have 

done. 

Dr. Dwelle (ASTHO) indicated that North Dakota has some challenges in the interoperability 

and bidirectional flow of immunizations between the Native American populations and the 

immunization registry. This is one area in which federal partners could encourage bidirectional 

flow. 

Vote: Second Half of General Recommendations 

Dr. Bocchini made a motion to approve the second half of the General Recommendations as 

presented, with the suggested language changes regarding ACA, YF after HCT, and IIS. Dr. 

Vázquez seconded the motion. The motion carried with 15 affirmative votes, 0 negative votes, 

and 0 abstentions. The disposition of the vote was as follows: 

15 Favored: Bennett, Belongia, Bocchini, Campos-Outcalt, Harriman, Harrison, Karron, 

Kempe, Pellegrini, Romero, Reingold, Riley, Rubin, Temte, and Vázquez 

0 Opposed: N/A 

0 Abstained: N/A 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Novel Influenza Vaccines 

Introduction 

Doug Campos-Outcalt, MD, MPA

Novel Influenza Vaccines Work Group 

Advisory Committee on Immunization Practices 

Dr. Campos-Outcalt reminded everyone that the ACIP Novel Influenza Vaccines WG was 

formed in February 2014, at which time the WG was charged with developing recommendations 

for use of influenza A (H5N1) vaccine during interpandemic periods. October 2014 ACIP 

meeting presentations included an update on influenza A (H5N1) epidemiology and vaccines, 

and GRADE and policy options for influenza A (H5N1) vaccine. A vote was planned for the 

February 2015 ACIP meeting; however, the Novel Influenza Vaccines session was cancelled 

due to impending inclement weather and was moved to the June 2015 meeting. 

Although a vote was intended during this session, in addition to the 2014 production delays 

following the Quebec plant inspection1

, additional delays were predicted for 2015-2016 due to 

manufacturing upgrades at that plant [

1

http://www.fda.gov/iceci/enforcementactions/ 

warningletters/2014/ucm401719.htm]. The current schedule is to produce a Q-Pan H5N1 lot in 

mid-2017]. Given the changing manufacturer’s schedule, an influenza A (H5) epidemiology 

update was presented and no recommended policy vote was entertained during this session. 

The WG will go into semi-hibernation and will be reconstituted closer to the time when the 

vaccine will be available. Any changes will be incorporated and recommendations for a vote 

will be brought forward at that time. 

Influenza A (H5) Epidemiology Update 

Sonja J. Olsen, PhD

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention 

Dr. Olsen provided an update on global epidemiology of H5N1 in humans and birds, an update 

on H5 found in US birds, and data on Q-Pan H5N1 cross-reactivity to some of these viruses. 

Since 2003, the Eurasian origin H5N1 viruses have spread in animals to 65 countries. As 

shown on the following map, H5N1 viruses have been found in birds in 20 countries in 2015: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

In three of the countries shown on the map (China, Egypt, and Indonesia), the virus has also 

been confirmed in humans in 2015. 

In the following graphic, the number of human H5N1 virus infections are shown by country 

between 2003 and 2015. Infections from each country are shown in a different color: 

Between November 2003 and May 1, 2015, there have been 840 cases in humans reported to 

the World Health Organization (WHO) from 16 countries. These cases have resulted in 413 

deaths, which is a mortality of 53%. In yellow at the right side are the recent cases, showing a 

large upsurge in H5N1 cases in humans in Egypt. This upsurge is the highest number of cases 

reported by a country in a similar time period. In 2015, there have been 132 cases in humans 

in Egypt. 

H5N1 viruses are now circulating in all sectors of poultry production throughout Egypt. This 

likely reflects changes in the economy and poultry industry. Many small farmers are raising 

poultry in a largely unmonitored and uncontrolled farming sector. The hemagglutinin (HA) gene 

continues to evolve; however, experts do not think the recent upsurge in human cases is due to 

changes in the virus. Instead, the increase in human infections is likely because of an increase 

in persons exposed to infected poultry. In the last month, cases have been decreasing. There 

have been fewer outbreaks in poultry, increased public health awareness, and probably some 

seasonal risk factors that are not fully understood. 

Another recent event is the detection of highly pathogenic avian influenza (HPAI) viruses in the 

US. In response to detection of HPAI H5N2 virus among commercial flocks in Canada in early 

December 2014, the US increased surveillance in wild birds along the US/Canada border and in 

the Pacific Flyway. Three novel viruses have now been found in wild birds and poultry in the 

US in commercial poultry and wild flocks: a new H5N1 reassortant1

, H5N8, H5N22. The H5N1 

virus is different from the Eurasian H5N1 virus. These three viruses in the US are highly 

pathogenic in chickens. They are reassortants viruses with an HA from a Eurasian H5N8 virus 

and are designated as a new Clade (2.3.4.4). The N2 and N8 are from a North American avian 

influenza. The neuraminidase is different from the strains causing illness and death discussed 

earlier [1

Different from Eurasian H5N1 virus causing human illness and death; 2N2 and N8 are 

different from strains circulating in Asia, Europe and Africa]. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The following table shows the number of HPAI H5 Detections in the US between December 14, 

2014 and June 9, 2015: 

Species H5N2 H5N8 H5N1 H5 

Poultry 218 4 

Captive Wild Bird 3 2 

Wild Bird (as of 5/14) 35 22 3 12 

Total # detections 256 28 3 12 

The United States Department of Agriculture (USDA) and states have mounted a very large 

response, responding quickly with quarantine, eradication with indemnity, monitoring, 

disinfecting, and testing to confirm virus-free premises. To date, over 47 million birds have 

been affected. 

The following map shows the geographic distribution of HPAI detections by H5 subtype: 

The blue circle in the Pacific Northwest is the location of the three H5N1 viruses detected in wild 

birds. The majority of detections are concentrated as a whole in two migratory pathways, the 

Pacific and the Mississippi Flyways. USDA scientists believe that wild birds introduced the 

viruses into commercial poultry. Although no humans have been infected to date, CDC is 

working with USDA and local and state health departments to monitor for illness in persons 

exposed to infected birds or contaminated surfaces. 

In terms of the number of HPAI avian influenza-infected premises detected between December 

10, 2014 and June 11, 2015, the majority of outbreaks (~90%) were detected in commercial 

poultry and chicken egg layers. Outbreaks may have peaked, as the number of detections has 

decreased in recent weeks. 

Given the changes in the epidemiology of H5N1 virus clades circulating globally and the 

detection of new H5 viruses in birds and poultry in the US, CDC wanted to determine whether 

the Q-Pan H5N1 vaccine cross-reacted with any of these viruses. There are no published data, 

but CDC was able to test a small number of sera from two vaccine studies—one from GSK and 

one from CDC. The sera were tested against viruses by microneutralization assay as this 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

assay is considered to be more sensitive than the HA inhibition assay. While these data are not 

currently published, they will be submitted for publication in the near future. 

CDC looked at the percent >4-fold increase in microneutralization antibody titers in Q-Pan 

H5N1 vaccine sera when challenged against other H5N1 viruses recently circulating in humans. 

Overall there was some cross-reactivity to the viruses. However, the response varied by clade. 

The response was fairly strong for the 2010 Egypt virus. Then CDC looked at the 

microneutralization antibody titers in Q-Pan H5N1 vaccine sera when challenged against the 

two new H5 viruses circulating in poultry in the US. The response was robust against the 

homologous vaccine strain, A/Indonesia/05/2005 (H5N1), was robust. In contrast, there was 

essentially no response to the two poultry viruses (H5N8 and H5N2). The data using vaccine 

sera from both the GSK and CDC studies showed similar results. 

H5 viruses are grouped into clades based on their phylogenetic characterization and sequence 

homology of the HA gene. The HA gene of H5N1 viruses evolves in nature. It has evolved into 

many genetically and antigenetically distinguishable clades. The H5 viruses in birds in the US 

are part of a newly designated clade 2.3.4.4. The following phylogenetic tree shows the 

evolutionary distance between those viruses and other viruses, including the Q-Pan H5N1 

vaccine shown toward the bottom of the graph: 

In other words, they are evolutionarily distant, and thus perhaps it is not surprising that there 

was no cross-reactivity. 

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Overall, it was found that the H5N1 Q-Pan vaccine offered some level of cross-neutralizing 

antibody titers to H5N1 viruses from various clades, including newly emerging strains. Crossclade responses vary between clades and viruses. The responses varied by clade and were 

generally lower that the response to the homologous vaccine strain. However, the response 

was robust to the clade 2.2.1 Egypt virus. In contrast, the vaccine (clade 2.1.3.2) elicited no 

neutralizing antibodies to the new H5N2 and H5N8 (clade 2.3.4.4) viruses found in poultry in 

the US. Additionally, where possible, evaluating cell-mediated cross-reactive immunity may be 

helpful to better understand the potential for vaccines to provide some level of cross-protection. 

In summary, HPAI H5N1 viruses continue to circulate globally and cause illness and death in 

humans. The most recent upsurge in Egypt was the result of increased poultry infections 

combined with increased interactions between infected birds and humans. The H5 viruses 

(H5N2, H5N8) in US birds are different from the Eurasian H5N1 viruses and thus far have not 

caused any illness in humans. Q-Pan H5N1 vaccine is cross-reactive with recently circulating 

Eurasian H5N1 viruses, but not with H5N2 or H5N8 in US birds. CDC is developing a 

candidate vaccine virus specific to the H5 viruses in the US that could be used to make a 

vaccine if one were needed. CDC and WHO will continue to monitor the global situation of 

avian influenza. 

Discussion Points 

It seemed surprising to Dr. Belongia that there have been so many flocks affected in the US 

over the past several months, but there have not been any instances of known transmissions to 

humans. He asked whether there were any ideas regarding why that might be the case. 

Dr. Olsen responded that CDC has been conducting some monitoring. Approximately 30 of 

1100 people, largely farm workers, have been exposed and gotten a respiratory illness. All of 

them have tested negative to date. It may be that the virus is not well-adapted, but the answer 

to why there has been no transmission to humans is not really known. 

Dr. Temte wondered whether the HAs in the three H5 viruses circulating in birds in North 

America were identical or similar. Regarding the graph showing the indication that the current 

avian epidemic in the US appears to be waning, he wondered whether there was an 

expectation that this would be on the upswing by October and whether anything is going to be 

done in terms of assuring poultry workers are vaccinated with appropriate seasonal influenza 

vaccine to reduce the risk of potential co-infection. In his state, a number of poultry workers 

tend to be people who may be undocumented and may be high risk individuals in terms of lack 

of usual medical assessments. It would be beneficial to be proactive. 

Dr. Olsen replied that the HA is similar, though she was not certain whether it was identical. In 

terms of the apparent waning of the current avian epidemic, the current thinking is that it may be 

decreasing in birds and poultry in the US. But, the expectation by USDA is that it will likely 

increase again in the fall because a seasonal pattern to these viruses has been observed 

globally for the Eurasian H5N1. There are recommendations for response workers to be 

vaccinated. Response workers include the 1100 farm workers, as well as approximately 2000 

to 4000 USDA direct hires and contractors who are response workers. There are written 

recommendations from the USDA for their response workers, including poultry cullers. She 

thought the former category (farm workers) was probably what Dr. Temte was referring to. 

There are US recommendations to vaccinate everyone 6 months of age and older. Although 

she did not know what specific states were doing in terms of outreach, CDC can find out. 

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Dr. Dwelle (ASTHO) found it interesting that none of these poultry infections were being 

observed in the wintering grounds of wild birds. They are migrating North at this point, and he 

wondered whether there was any indication of why this was occurring in those reaching their 

summer nesting grounds. 

Dr. Olsen replied that the viruses have different prevalences in different species and can affect 

them differently. Some viruses cause overt clinical illness and some do not. Ongoing 

surveillance and/or testing only birds that die may be factors. 

Dr. Sun (FDA) noted that in assessing cross-neutralization with the H5N1 sera in humans 

against the avian H5 strain, nothing was found. He asked whether HA inhibition assay was 

utilized to determine whether there was cross-neutralization. 

Dr. Olsen responded that CDC did not use that assay. They used only the microneutralization 

assay because it is accepted to be a more sensitive assay. They thought they would be more 

likely to find something with the microneutralization assay than the HA inhibition assay, so they 

did not test using the HA inhibition assay. 

Dr. Temte reminded everyone that this WG would remain dormant until vaccine becomes 

available. The decision was that they did not want to have an approved recommendation with 

no ability to provide vaccine. 

Influenza Vaccines 

Introduction 

Ruth Karron, MD 

Chair, Influenza Work Group 

Dr. Karron reported that since June 2014, the Influenza WG has focused primarily on 2013­

2014 vaccine effectiveness estimates for live attenuated influenza vaccine (LAIV) and 

inactivated influenza vaccine (IIV). They have heard data from the US Flu VE Network, the 

Armed Forces Health Surveillance Center, and MedImmune on a post-marketing study of 

quadrivalent LAIV. She indicated that during this session, updates would be presented on 

influenza vaccine effectiveness, quadrivalent intradermal influenza vaccine, influenza vaccine 

safety, and high-dose influenza vaccine. 

Influenza Vaccine Effectiveness Update 

Brendan Flannery, PhD 

Influenza Division 

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

Dr. Flannery presented preliminary end-of-season estimates of influenza vaccine effectiveness 

for the 2014-2015 season from the US Flu Vaccine Effectiveness Network. Data were provided 

by US Flu VE Network sites and were analyzed at CDC by Jessie Clippard, Data Manager. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Based on influenza surveillance data from US public health sites comparing the 2014-2015 

season with the two previous seasons, influenza A(H3N2) virus predominated during 2014­

2015 as it did in 2012-2013, with circulation of influenza B virus during the second half of the 

season after January. Influenza A(H1N1)pdm09, which predominated during 2013-2014 

season, circulated at very low levels in 2014-2015. Thus, there were no additional data to 

provide on VE for the H1N1 virus. 

The five institutions and Principal Investigators (PIs) participating in the US Flu VE network are 

as follows: 

 Group Health Cooperative: PIs Lisa Jackson and Mike Jackson 

 Baylor Scott and White Health: PI Manju Gaglani 

 Marshfield Clinic Research Foundation: PIs Ed Belongia and Huong McLean 

 University of Michigan: PIs Arnold Monto and Suzanne Ohmit 

 University of Pittsburgh: PIs Rick Zimmerman and Patricia Nowalk 

As a reminder, methods for the Flu VE Network have been presented previously. This analysis 

includes outpatients enrolled from November 10, 2014 through April 10, 2015, when influenza 

cases were identified at the five VE network sites. VE is estimated from the odds ratios 

comparing vaccination among influenza virus-positive case patients to influenza virus-negative 

patients as the comparison group. Influenza virus was tested using polymerase chain reaction 

(PCR). Vaccination status was determined as for interim estimates. Partially vaccinated 

children are excluded from this analysis. 

This season for the first time, it was possible to estimate VE for specific groups of H3N2 viruses 

classified by HA gene relatedness. Hemagglutination inhibition (HI) assays are normally used 

to characterize circulating influenza viruses as “vaccine-like” or “low reactors” to vaccine as a 

measure of antigenic difference or drift. Most, or more than 80%, of the H3N2 viruses tested at 

CDC by HI were low reactors or antigenically drifted from the 2014-2015 vaccine component 

A/Texas/50/2012. In addition, many H3N2 viruses could not be characterized by HI due to 

changes in the properties of the virus. As a result, CDC used genetic sequencing to 

characterize H3N2 viruses and inferred antigenic properties based on viruses that could be 

characterized by HI. Several genetic groups of H3N2 viruses co-circulated during the season, 

providing the opportunity to compare VE by genetic group. VE by genetic group is calculated 

the same way as for all influenza viruses, except that cases are restricted to a specific HA 

genetic group. 

It was a banner year for the Flu VE network. A total of 9707 patients were enrolled at the five 

VE network sites, including over 3700 children and adolescents and 1200 patients 65 years of 

age and older. Overall, 24% of those enrolled tested positive for influenza by reverse 

transcription polymerase chain reaction (RT-PCR) and 76% were RT-PCR-negative. Of the 

influenza cases, 83% were type A and all subtyped A viruses in the network were H3N2. 

Among the 17% of enrollees who tested positive for influenza B virus, 85% were the BYamagata lineage that is in both the trivalent and the quadrivalent vaccines and 15% were BVictoria lineage included in quadrivalent vaccines. Overall, 53% of patients were considered 

vaccinated. Among vaccine types, 51% of all inactivated vaccines were quadrivalent, 49% 

trivalent. Live-attenuated vaccine accounted for 26% of vaccines among 2 through 17 year 

olds, and 9% of vaccinated patients 65 years and older received high-dose vaccine. 

In terms of numbers of patients enrolled per week by RT-PCR result, peak enrollment for H3N2 

cases occurred in December during weeks 50 through 52. Numbers of influenza B cases were 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

low, with only a slight increase in March. The overall adjusted VE against any influenza virus 

was 23% and was statistically significant. VE ranged from 10% (non-significant) among 18 

through 49 year olds to 36% (significant) among patients 65 years and older. For patients of all 

ages combined, adjusted VE for any influenza vaccination was 13% against H3N2, 55% against 

B-Yamagata, and 63% against B-Victoria. VE estimates were similar across age groups with 

overlapping confidence intervals. For H3N2, VE was low in all age groups and confidence 

intervals crossed zero for all age groups except young children. VE against influenza B virus 

was higher with some smaller sample sizes leading to large confidence intervals. The highest 

point estimate was seen in patients 65 years and older. 

Low VE against H3N2 viruses was consistent with predominance of one genetic group, 3C.2a, 

among H3N2 viruses sequenced from US laboratories or from the US Flu VE network. Most 

viruses tested from the predominant genetic group were low reactors to vaccine by HI. A 

smaller percentage of viruses belonged to groups 3C.3 or 3C.3b, which were characterized by 

HI as vaccine-like. Of note, although only 3% of sequenced viruses belonged to group 3C.3a, 

which includes the A/Switzerland virus chosen as the H3N2 component of the 2015-2016 

vaccine, groups 2a and 3a share antigenic properties. With the sequenced viruses from the US 

Flu VE network, it was possible to estimate VE against the predominant genetic group of 

antigenically drifted H3N2 viruses and one vaccine-like genetic group, 3C.3b. Compared to VE 

against all H3N2 genetic groups combined, VE against the more vaccine-like group 3b viruses 

was 43% and statistically significant, while VE against the antigenically drifted group 2a viruses 

was not significant. 

Regarding VE against any influenza by vaccine type, adjusted VE for quadrivalent liveattenuated vaccine against any influenza was 9% overall with confidence interval including 

zero, with similar estimates for younger and older children. Adjusted VE for inactivated vaccine 

against any influenza was 31% and was statistically significant. Adjusted VE against H3N2 

among 2 through 17 year olds was slightly lower at -8% (-44% to 19%) for LAIV and 17% (-4 to 

33%) for inactivated vaccines. Results were similar when the comparison was limited to 

quadrivalent inactivated vaccines and medical record documented doses: 

 Quadrivalent inactivated, IIV4, 892 (45%) 

 Trivalent inactivated, IIV3, 560 (28%) 

 Quadrivalent live-attenuated, LAIV4, 509 (26%) 

In terms of the comparison by influenza type and B lineage, adjusted VE estimates against 

H3N2, B, or B/Yamagata lineage were similar for IIV and LAIV. VE was low for H3N2 for both 

vaccine types, and neither was statistically significant. VE against influenza B and B/Yamagata 

was higher for both IIV and LAIV. 

VE was also compared for high-dose and standard-dose inactivated vaccines compared to 

unvaccinated among patients 65 years of age and older. However, these estimates were not 

adjusted for comorbid, high-risk conditions. VE for high-dose vaccine against any influenza was 

14% and was not statistically significant. VE for any standard-dose inactivated vaccine was 

31% and for trivalent standard dose vaccine was 38%, and both were statistically significant. 

VE against H3N2 was lower for both vaccine types and was not significant, and relative 

effectiveness of high-dose to standard dose showed no significant difference between the two 

vaccine types. These are preliminary data. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

There are several important limitations. Some estimates are imprecise due to small numbers of 

patients in specific groups (e.g., VE for high-dose, VE for live-attenuated by age group, and VE 

for less common H3 genetic groups). As customary with an observational study design, there is 

a potential for confounding due to differences in patient characteristics among vaccinated/ 

unvaccinated or by vaccine type. 

In conclusion, reduced VE is consistent with predominance of antigenically drifted A(H3N2) 

viruses. H3N2 accounted for 83% of influenza-positive cases at US Flu VE Network sites. The 

majority (>80%) in the predominant HA genetic group 3C.2a were characterized as low reactors 

to vaccine. There was higher VE against less prevalent vaccine-like A(H3N2) viruses and 

influenza B viruses. VE was 66% to 67% against influenza B for LAIV and IIV, respectively, 

among children and adolescents. There was reduced or non-significant VE against A(H3N2) for 

any vaccine type, including LAIV and IIV in children, as well as high-dose and standard-dose 

among persons ≥65 years of age. 

Discussion Points 

Dr. Karron recalled the low VE of approximately 43% for 156 cases against H3N2 for vaccinelike strains belonging to HA group 3C.3b. She wondered whether LAIV could be split out for the 

viruses that were like the ones in the vaccine. 

Dr. Flannery replied that the estimate against the genetic groups that were vaccine-like for LAIV 

and IIV were both higher, which is similar to what he showed for all age groups. Neither 

estimate is significant compared to the unvaccinated group. It is just that the sample sizes are 

small. This is consistent with the same trend observed for any vaccine for which LAIV and IIV 

seem to have better effectiveness against the vaccine-like virus than against the drifted viruses 

belonging to HA group 3C.2a. 

Regarding vaccine effectiveness by age group, Dr. Sun (FDA) thought it seemed like 18 

through 49 years olds have the lowest VE. He wondered whether that was because most 

strains are unmatched and if that explained the low efficacy in the middle age group. 

Dr. Flannery said he did not have an explanation for this, and that it was not as simple as a 

difference in distribution by genetic group. The pattern looks very similar for just H3N2s, but it 

was not broken down by vaccine-like and non-vaccine-like groups. Even the early estimates 

were lower for the 18 through 49 year old group, but the reason is unknown. 

Dr. Gemmill (NACI) wondered whether it could be surmised that the reduced VE for LAIV that 

was presented in October was well behind them, and if Dr. Flannery could make any comments 

about that. 

Dr. Flannery responded that the only reduced effectiveness observed during the 2013-14 

season was against the H1N1 pandemic strain. There was not enough pandemic H1N1 virus 

circulation in 2014-15 to have an estimate for LAIV against H1N1. MedImunne presented data 

which suggested that LAIV effectiveness in 2013-14 was good against B. These data are 

consistent with good effectiveness against B in 2014-15, but are not helpful at all with more 

information about H1N1. VE against H3N2 was not very good for either vaccine this year with 

this much antigenic drift. 

Dr. Decker (Sanofi Pasteur) observed that they were asking an interesting set of questions from 

the data, but were not getting robust answers back because of the sample size limitations. He 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

asked whether there was hope that in the future the surveillance population would be 

expanded. 

Dr. Flannery replied that the question for ACIP in the past has regarded how well the vaccine is 

working overall. There is increasing interest in breaking out vaccine type, and for the first time 

there are data comparing high-dose versus standard-dose. The analyses are also dependent 

upon uptake of the various vaccines. In the last several years, there have been estimates for 

LAIV and this is the first year that an estimate could be presented for high-dose. As new 

vaccines are introduced, it is going to be very difficult to increase sample sizes and keep up 

with the vaccines. There are no plans to expand the network with the objective of trying to 

estimate vaccine type-specific VE estimates, but the numbers enrolled are being increased to 

assess the types of estimates presented in the past against what circulates by age group and 

some of the predominant vaccine types. 

Dr. Schuchat added that it is extraordinary how much data there are by age, vaccine type, and 

serotype in June. There were also a lot of data in January. Ten years ago, these types of data 

would be provided overall two or three years after the season. It is extremely helpful to have 

this large a sample size now for children and the elderly, and it is very useful for ACIP to be 

able to reflect on it. It does not mean that the answers are going to be clear with clean, tight 

confidence intervals. But with a moderate to low efficacy product, even with a very large 

sample size, the confidence intervals might not be clear. 

Dr. Belongia pointed out that it was an understatement to call this “surveillance.” This is a 

highly resource-intensive activity that requires many people and resources yearly. It is clearly 

paying off in terms of data and utility. 

Dr. Sawyer (PIDS) commented that pediatricians and young children of the world are hanging 

on ACIP’s every word about LAIV effectiveness. There was a preferential statement. Now 

there is not a preferential statement. The point estimates make him wonder whether it is now 

inferior for some reason. He sees that the confidence intervals are very wide, but he would 

hope that there might be some opportunity to tighten those confidence intervals for that age 

group in order to resolve the uncertainty pediatricians are facing this year in trying to determine 

which vaccine to use. 

To underscore Dr. Schuchat’s comments, Dr. Baker (IDSA) noted that most hospitals are not 

currently performing viral cultures. This kind of work cannot be done without isolates. They are 

using PCR and indicate A or B at most. She agreed that the amount of data available is 

incredible. It is imperative in the molecular era, in virology, to have viable virus isolates, 

especially with influenza. 

Wayne Hachey (Protein Sciences Corporation) reported that Protein Sciences Corporation 

conducted a clinical trial during this season in adults over 50 years of age. Those results 

became available about 24 hours before this meeting. Preliminarily, in the over 50 group, the 

attack rate was 50% less than the comparator. Whether it is having three times the amount of 

antigen or not having to deal with an egg-grown vaccine virus is unknown, but it does appear 

that the vaccine was reasonably effective during this past influenza season. For the subgroup 

75 years of age and older, the attack rate with the comparator was 40% and with Flublok® was 

25%. They will share additional data with the WG as it becomes available. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Quadrivalent Intradermal Influenza Vaccine 

Corey Robertson, MD, MPH

Sanofi Pasteur 

During this session, Dr. Robertson presented an update on Fluzone Intradermal® quadrivalent 

vaccine (QIV-ID). In 2010, Sanofi Pasteur first introduced the intradermal influenza vaccine to 

the US in a trivalent formulation. The quadrivalent formulation was licensed in December 2014. 

For the 2015-2016 season and beyond, Fluzone Intradermal® will be available only in a 

quadrivalent formulation. Doses will be available for the upcoming season. For those 

unfamiliar with the Fluzone® intradermal vaccine, Dr. Robertson shared the following image of 

the microinjection system used for Fluzone Intradermal® quadrivalent: 

The microinjection system consists of a ready-to-use, prefilled syringe that does not require air 

purging and contains a 0.1 mL dose of vaccine. Probably the most salient feature of the 

microinjection system is the feature that is barely visible—the microneedle that is pre-attached 

to the syringe. This microneedle is 30-gauge in diameter and about 1.5 millimeters in length, 

which is about the width of a penny. The length of this microneedle ensures that the vaccine is 

deposited within the dermal layer of the skin of young adults regardless of their gender, race, or 

body mass index (BMI). Another component of the microinjection system is the integrated 

needle shield that can be activated after vaccination. This needle shield covers the 

microneedle and may help reduce the risk of injury to healthcare personnel. 

Years ago, Sanofi Pasteur conducted studies to show that the trivalent formulation of Fluzone 

Intradermal® vaccine induced immune responses that were comparable to the Fluzone® vaccine 

that is injected intramuscularly. Building upon that experience, Sanofi Pasteur embarked upon 

a clinical development program that consisted of a Phase 3 clinical trial, which is referred to as 

QID01. This was a randomized, double-blind, active-controlled trial that was conducted in 

multiple centers across the US during the 2012-2013 influenza season. More than 3300 adults 

18 through 64 years of age participated in the trial, and they were randomly assigned to receive 

one of the three study vaccines: QIV-ID or either one of two trivalent intradermal controls. All 

of the study vaccines contained the same A strains, but they differed with respect to their B 

strain compositions as shown in the following table: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

IIV4-ID 

N=1676 

IIV3-ID(1)

N=837 

IIV3-ID(2)

N=847 

A/Brisbane/59/2007(H1N1) 

A/Uruguay/716/2007(H3N2) 

B/Texas/6/2011 (Yamagata) 

B/Brisbane/60/2008 (Victoria) 

A/Brisbane/59/2007(H1N1) 

A/Uruguay/716/2007(H3N2) 

B/Texas/6/2011 (Yamagata) 

A/Brisbane/59/2007(H1N1) 

A/Uruguay/716/2007(H3N2) 

B/Brisbane/60/2008 (Victoria) 

Each vaccine was formulated to contain 9 micrograms of hemagglutinin per strain per 0.1 mL 

dose, and each subject received his or her assigned vaccine on Day 0 of the study. 

Data were collected for safety and immunogenicity as is typically done in Sanofi Pasteur’s 

influenza vaccine clinical trials. Monitoring was done for immediate reactions within 30 minutes 

after vaccination, solicited reactions within 7 days after vaccination, unsolicited AEs within 28 

days after vaccination, and SAEs within 6 months after vaccination. HAI responses were 

assessed by collecting specimens before and approximately 28 days after vaccination. About 

two-thirds of the trial population was randomly selected to participate in the immunogenicity 

assessment. The endpoints were post-vaccination GMTs, seroconversion rates, and 

seroprotection rates. 

Regarding the study results, injection-site pain was the most commonly reported injection site 

reaction among all vaccine groups. Vaccine rates of pain, pruritus, and erythema at the 

injection site were comparable across the three vaccine groups. Reactions were primarily 

Grade 1 or 2 in intensity and were self-limiting. A similar pattern was observed for injection site 

reactions of swelling, induration, and ecchymosis, albeit at frequencies that were far lower than 

for pain, pruritus, and erythema at the injection site. 

In terms of solicited systemic reactions, approximately one-third of the participants in each 

vaccine group experienced myalgia, headache, or malaise. Fever was a rare occurrence in the 

study, with less than 1% of participants in each vaccine arm experiencing that outcome. Rates 

of unsolicited AEs and SAEs were comparable across the three vaccine groups. One death 

was reported in this study, which occurred in a 60 year old man who had risk factors for 

coronary disease. He had a fatal myocardial infarction on Day 177 of the 180-day safety followup period. At rates of about 20%, comparable proportions of quadrivalent and trivalent 

recipients experienced either a Grade 2 or Grade 3 solicited systemic reaction. Likewise, 

comparable proportions of QIV and trivalent recipients experienced a Grade 3 solicited injection 

site reaction, at 4% and 3.1%, respectively. 

With respect to immunogenicity, post-vaccination GMTs+ 28 days after vaccination for the 

quadrivalent formulation were comparable to those observed for the trivalent controls for all four 

vaccine strains. For the B strain responses following use of the trivalent controls that did not 

contain both B strains, the GMT responses were about half of those observed for the 

quadrivalent formulation. Based on predefined criteria, QIV-ID induced immune responses that 

were non-inferior to the trivalent controls with respect to all four vaccine strains and B strain 

responses were superior to the trivalent controls that did not contain those corresponding B 

strains. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The quadrivalent formulation induced seroconversion rates that were comparable to those seen 

following use of the trivalent controls for corresponding strains. Similar to what was observed 

with the GMT responses, seroconversion rates following use of the trivalent controls for the B 

strains that were not contained in the trivalent controls were about half of those seen for the 

quadrivalent formulation. The quadrivalent formulation met all nine inferiority and superiority 

endpoints. 

In conclusion, Fluzone® Intradermal quadrivalent vaccine was as immunogenic and as safe as 

trivalent intradermal vaccine in a healthy adult population. With inclusion of the second B strain, 

Fluzone® Intradermal quadrivalent vaccine reduced the risk of B strain mismatch and could help 

provide improved protection against influenza. 

Discussion Points 

Dr. Zahn (NACCHO) asked whether other parts of the immune response are similar or 

fundamentally different for IIV versus intradermal. 

Dr. Robertson replied the cell-mediated immunity has been a challenge to assess, and 

unfortunately there is not currently an answer to whether use of the intradermal vaccine might 

have another mechanism of action in terms of inducing an immune response. 

Ms. Hayes (ACNM/ANA) said it was her understanding that this is the only FDA Category A 

influenza vaccine, and that there have been clinical trials among pregnant women proving 

safety. 

Dr. Robertson responded that this is a Category B vaccine. 

Dr. Sun (FDA) added that the pregnancy categories will be eliminated and there will be a new 

way to approach labels with regard to pregnancy. 

Dr. Reingold asked why it took two years to provide the results from the trial conducted during 

the 2012-2013 influenza season. 

Dr. Robertson replied that it was because it took that long to conduct the clinical trials and 

license the product. 

Influenza Safety Update 

Tom Shimabukuro, MD, MPH, MBA 

Immunization Safety Office

Division of Healthcare Quality Promotion 

National Center for Emerging and Zoonotic Infectious Diseases

Centers for Disease Control and Prevention 

Dr. Shimabukuro presented an end-of-season update on 2014-2015 influenza vaccine safety 

monitoring based on the Vaccine Adverse Event Reporting System (VAERS) surveillance, the 

Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA), and a recent VSD study that 

assessed trivalent inactivated influenza vaccine and spontaneous abortion. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

As a reminded, VAERS is a spontaneous reporting system, which is co-administered by CDC 

and FDA. The strengths and limitations of VAERS are those inherent to passive reporting 

systems in general, including the following: 

Strengths 

 Rapid signal detection 

 Can detect rare adverse events 

 Generates hypothesis 

 Encourages reports from healthcare 

providers and accepts reports from patients 

and others 

 Data available to the public 

Limitations 

 Reporting bias (e.g., underreporting, 

stimulated reporting) 

 Inconsistent data quality and completeness 

 Not designed to assess if vaccine caused 

an adverse event (AE) 

 Lack of unvaccinated comparison group 

For VAERS surveillance, US influenza vaccine reports received through May 22, 2015 were 

assessed for individuals who were vaccinated from July 1, 2014 through May 1, 2015. Signs, 

symptoms, and diagnoses were coded using the Medical Dictionary for Regulatory Activities 

(MedDRA) terms. VAERS reports and medical record reviews were conducted for all serious 

reports following IIV4, LAIV4, ccIIV3, or RIV3; all anaphylaxis reports in persons with a history 

of egg allergy; and pregnancy reports for spontaneous abortion, stillbirth, congenital anomalies, 

and serious reports. Empirical Bayesian data mining was conducted by colleagues at FDA 

[Banks et al. Comparing data mining methods on the VAERS database. Pharmacoepidemiol 

Drug Saf. 2005;14:601–609]. 

In terms of US reports to VAERS following IIV3, IIV4, LAIV4 and IIV3-HD, serious reports for all 

vaccines and vaccine types ranged from about 5% to 6%. Guillain-Barré Syndrome (GBS) 

reports for all vaccines and vaccine types did not exceed 1%, and anaphylaxis reports were 

rare. This is similar to data from previous seasons for these vaccines and vaccine types. There 

were no confirmed anaphylaxis reports with a history of documented egg allergy, and no data 

mining findings for GBS or anaphylaxis. The numbers were smaller for cell-culture IIV3, 

recombinant influenza vaccine, and intradermal vaccine. This likely represents lower uptake of 

these vaccines. Overall, the results were similar to the results for other vaccines and vaccine 

types. However, the percentages are somewhat more influenced by small numbers. There 

were no confirmed anaphylaxis reports with a history of documented egg allergy and no data 

mining findings for GBS and anaphylaxis. 

Regarding pregnancy reports in VAERS following influenza vaccination, there were 85 total 

reports after IIV3 or IIV4. In most of these reports, vaccination occurred during the first or 

second trimester. In 27% of the reports, a non-pregnancy-specific AE was reported such as an 

injection site reaction. In 64%, no AE was reported. That total combined is 91% that were not 

pregnancy-specific. Eight reports had pregnancy-specific outcomes, including six spontaneous 

abortions, one stillbirth, and one report of vaginal bleeding. There were 18 total reports after 

LAIV4. As a reminder, LAIV is not recommended during pregnancy. No AEs were reported for 

17 of those 18 reports, and there was one report of spontaneous abortion. 

In summary, no new safety concerns were detected for IIVs, LAIV4, cell-culture IIV, or 

recombinant vaccine during the 2014-2015 influenza season. Surveillance for the 2015-2016 

influenza season will include enhanced safety monitoring (i.e., clinical review of reports and 

medical records for selected reports) for Quadrivalent vaccines (IIV4 and LAIV4), ccIIV, and 

RIV3; pregnancy reports; and reports in persons with history of egg allergy. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Moving on to VSD-RCA for the past season, as a reminder the VSD is a collaboration between 

CDC and nine integrated healthcare plans that collects data on over 9 million persons per year, 

or approximately 3% of the US population. The VSD links vaccination data to health outcomes 

data. Its strengths and limitations are as follows: 

Strengths 

 All medical encounters are available 

 Vaccine registry data 

 Can calculate rates 

 Can assess risk of an AE 

 Can review medical records 

 Tested algorithm to identify pregnancies 

 Annual birth cohort = 100k 

Limitations 

 Sample size may be inadequate for very 

rare events 

 Vaccines administered outside of medical 

home may not be captured 

 Medically unattended health events not 

captured 

 Potential for lack of socioeconomic 

diversity 

 Data lags 

The RCA outcomes for the past season include anaphylaxis, Bell’s palsy, encephalitis, GBS, 

seizures, and transverse myelitis. Age groups, risk window, and control window are also 

included for the self-controlled design. As a reminder, there are two RCA designs. The selfcontrolled RCA design means that a person serves as his or her own control and it assesses 

cases in the risk window versus cases in the comparison window. The current versus historical 

design assesses a current group of patients compared to a historical group of comparison 

patients. The comparison window could be before or after the risk window. 

In terms of Dose 1 doses administered for specific vaccines, IIV3 dominates for all ages at 3.4 

million doses. There are smaller numbers for IIV4 (251,271), LAIV4 (307,967), and high-dose 

(103,121). For the subset of doses administered to children 6 through 23 months of age, there 

were 73,000 IIV3 doses and 86,000 IIV4 doses. 

Regarding signal detection and evaluation for two of the outcomes, Bell’s palsy and 

encephalitis, the current versus historical design signaled for Bell’s palsy in patients 50-plus 

years of age following IIV4 in October 2014. This is an automated International Classification of 

Diseases (ICD)-9 code-based analysis. However, after chart review of cases, it was 

determined to be a false signal. The current versus historical and self-controlled risk interval 

designs both signaled for encephalitis following IIV3 in December 2014. No significant 

clustering was found within the 1- to 21-day risk window. After a chart review of cases, it was 

determined to be a false signal. 

For the outcome of seizures, the self-controlled risk design signaled for seizures in children 6 to 

23 months old following IIV3 in December 2014. Dr. Shimabukuro explained that the reason 

“signals” was shown in quotation marks was because this technically was not a signal. This 

association has been observed in previous influenza seasons, so it is not a new safety concern. 

Over 73,000 total IIV3 Dose 1 doses were administered. Five events occurred in the risk 

window, and one event occurred in the comparison window. The relative risk was 17.5, which 

was statistically significant. The self-controlled risk interval design had a non-statistically 

significant elevated relative risk for seizures in children 6 to 23 months old following IIV4. Just 

over 86,000 Dose 1 doses were administered. There were eight events in the risk window and 

eight in the comparison. The relative risk of 3.5 was not statistically significant, but approached 

the critical value of the log likelihood ratio. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

To evaluate the increased risk of seizures following IIV3, the data were combined for the 2014­

2015 and 2013-2014 influenza seasons. This is the same formulation for the 6- to 23-month old 

age group. That resulted in a total of 244,000 total IIV3 Dose 1 doses administered to this age 

group. For IIV3 +/- other vaccines, which could include PCV13, the relative risk was 2.5 and 

was statistically significant. For children who received IIV3 + PCV13 +/- other vaccines during 

the same healthcare visit, the relative risk was 5.3, which is statistically significant. For IIV3 +/­

other vaccines, but not PCV13, and for IIV3 given alone, the relative risk was not significant. 

In summary, signals were detected for Bell’s palsy and encephalitis. Both were ruled out for 

true signals after a chart review of the cases. A statistically significant elevated relative risk was 

detected for seizures in children 6- to 23-months of age following IIV3, and there was a nonstatistically significant elevated risk following IIV4. Further assessment indicated that the risk 

was highest when IIV3 or IIV4 was administered together with PCV13, and was highest in 

children 12- to 23-month olds, as has been observed in previous seasons. 

A VSD study was led by Dr. Jim Donahue, et al. at the Marshfield Clinic titled, “Evaluating the 

risk of spontaneous abortion following administration of influenza vaccines containing 

H1N1pdm09 and H3N2 viral antigens.” As a reminder, ACIP has recommended seasonal 

influenza vaccination for women in all stages of pregnancy since 2004. Available data indicate 

that IIV is safe during pregnancy. However, limited data exist on IIV safety in the first trimester 

of pregnancy. Uptake of influenza vaccine in pregnancy increased during the 2009-2010 

pandemic influenza season, as well as in subsequent influenza seasons. 

Spontaneous abortion (SAB) is a relatively common outcome of pregnancy. SAB is the 

spontaneous loss of a fetus before the 20th week of pregnancy. Pregnancy losses after the 20th 

week are referred to as stillbirths. SAB occurs in 15% to 20% of women who know they are 

pregnant. Most SABs occur during the first seven weeks of pregnancy. The risk factors for SAB 

include advanced maternal age, smoking, obesity, autoimmune disease, and prior SAB. In a 

previous case-control study in the VSD in 2005-2006 and in 2006-2007, no association was 

found with SAB and IIV31

. A recent meta-analysis did not find an association between SAB and 

monovalent H1N1 vaccination2

. The results of these studies and the meta-analysis were not 

available when the current VSD IIV3-SAB study was initiated. The largest study in the metaanalysis involved adjuvanted influenza vaccines. Other studies of seasonal IIV3 in pregnancy 

and SAB have been reassuring3 [

1

Irving et al. Obstet Gynecol. 2013 Jan;121(1):159-65; 

2

Bratton et al. Clin Infect Dis. 2015 Mar 1;60(5):e11-9; 3McMillan et al. Vaccine. 2015 Apr 

27;33(18):2108-17; Chambers et al. Vaccine. 2013 Oct 17;31(44):5026-32; Moro et al. Am J 

Obstet Gynecol. 2011 Feb;204(2):146.e1-7; Moro et al. Am J Obstet Gynecol. 2011 

Nov;205(5):473.e1-9]. 

Using similar methods to the previous VSD study (2005-2007 data), Donahue et al. conducted a 

study to assess whether IIV3 containing the influenza A (H1N1) pandemic antigen was 

associated with SAB during the combined 2010-2011 and 2011-2012 influenza seasons. The 

primary objective was to estimate the association of SAB with IIV3 in a 28-day risk window. 

The IIV3 formulation was the same during both seasons and contained the influenza A (H1N1) 

pandemic antigen. Specifically, the formulation for 2010-2011 and 2011-2012 influenza 

seasons included the following: 

 A/California/7/09 (H1N1)-like virus (pandemic (H1N1) 2009 influenza virus) 

 A/Perth/16/2009 (H3N2)-like virus 

 B/Brisbane/60/2008-like virus 

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Regarding the preliminary results, there were 485 matched pairs in the final combined analysis. 

The adjusted odds ratio was 2.0 with a 95% confidence interval of 1.1 to 3.6 for IIV receipt in 

the 1 to 28 days before SAB compared to unvaccinated women. There was no association in 

other risk windows. A post-hoc analysis of the 1- to 28-day window was conducted to assess 

season-specific analyses. For the 2010-2011 season, the adjusted odds ratio was 3.7 with a 

95% confidence interval of 1.4 to 9.4. In the 2011-2012 season, the adjusted odds ratio was 

1.4 with a 95% confidence interval of 0.6 to 3.3 and was not significant. As a reminder, the 

vaccine formulation was the same in both seasons. 

 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The primary objective was to estimate the association of SAB with IIV3 in a 28-day risk window. 

The IIV3 formulation was the same during both seasons. This was a matched case-control 

design using a 1:1 matching ratio. Cases were women with SAB from 5 to less than 20 weeks 

gestational age. Controls were women with live births or stillbirths >20 weeks gestational age. 

SAB was identified using ICD-9 codes confirmed through medical record abstraction and 

adjudicated to confirm SAB and SAB date. The date of SAB was the reference date for each 

case-control pair. Cases and controls were matched on age (<30, 30+ years), VSD site, and 

last menstrual period (LMP). Eligibility criteria included the following: 

 Women 18 to 44 years old 

 Enrolled ≥1 year prior to LMP 

 LMP documented in record 

 Confirmed intrauterine pregnancy by ultrasound 

Vaccine exposure included receipt of IIV3 documented in the medical record. The risk window 

was 28 days before the reference date, although the investigators also examined risk windows 

beyond 28 days. Conditional logistic regression was conducted and included the following 

covariates: 

 Maternal age 

 Smoking during pregnancy 

 History of type 1 or 2 diabetes mellitus 

 Concomitant IIV3 and Tdap vaccination 

 Pre-pregnancy body mass index 

 Previous healthcare utilization 

Also assessed was the association between SAB and IIV3 in a 1- to 28-day risk window 

restricted to women who received pH1N1-containing vaccine in the previous season. A 

H1N1pdm09-containing vaccine in the previous season could have been the monovalent or 

trivalent vaccine depending upon the season. For women who received a H1N1pdm09 ­

containing vaccine in a previous season and were vaccinated in the current season, the 

adjusted odds ratio was 7.7 with a confidence interval of 2.2 to 27.3. For women who did not 

receive a H1N1pdm09-containing vaccine in the previous season and were vaccinated in the 

current season, the adjusted odds ratio was 1.3 and was not statistically significant. 

This study was subject to some limitations. The findings of effects of prior H1N1 vaccination 

were post-hoc secondary analyses. The study was not powered for the secondary analyses 

and although some relative risks were high, the confidence intervals were very wide. This is an 

observational study, which is subject to possible biases and confounding. It is possible that 

vaccinated women who had SABs were more likely to come to medical attention. It was not 

possible to include potential risks from influenza infection. There may be other unmeasured 

confounding factors as well. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The results of the VSD IIV3-SAB study suggest an increased risk of SAB in some pregnant 

women in the 1 to 28 days after receiving IIV3 during the combined 2010-2011 and 

2011-2012 seasons. The risk was not increased in risk intervals more than 28 days after 

vaccination. An increased risk was observed in 2010-2011, but not in 2011-2012 when 

disregarding prior season vaccination with a H1N1pdm09-containing vaccine. In both seasons, 

increased risk was seen in women who had also received a H1N1pdm09-containing vaccine in 

the previous season, but not in women who did not receive a pH1N1-containing vaccine in the 

previous season. 

It is important to note that these findings are preliminary and are inconsistent with prior research 

on IIV safety and pregnancy, including the prior VSD study and meta-analysis previously 

described. However, these studies did not evaluate the effect of prior vaccination. CDC plans 

to follow up on this finding for SAB following IIV3 with additional research in the VSD, and plans 

to replicate the study in more recent influenza seasons to assess the effect of prior vaccination 

with H1N1pdm09-containing vaccines as a primary objective. An attempt also will be made to 

evaluate the risk of SAB from influenza infection. 

In conclusion, no new safety concerns during the 2014-2015 influenza season have been 

detected through VAERS surveillance. An elevated relative risk was detected in the VSD RCA 

for seizures following IIV3 and IIV4 in children aged 6 to 23 months. In terms of the VSD casecontrol study of SAB following IIV, the preliminary results from the 2010-2011 and 2011-2012 

seasons show an increased risk of SAB following IIV3 among pregnant women in the 1- to 28­

day risk window who had received a pH1N1-containing vaccine the prior influenza season. 

These findings are inconsistent with prior studies assessing IIV3 and SAB, and follow-up 

studies are planned. 

Discussion Points 

Noting that more than half of first-time miscarriages are associated with chromosomal 

abnormality, few patients accurately remember the date of their LMP, and especially first 

trimester ultrasounds are dependent upon the skill of the person doing them, Dr. Riley 

wondered what the mechanism would be to explain this finding. 

Dr. Shimabukuro responded that the biological mechanism for this finding is unknown. In 

general, vaccination causes an inflammatory response. This is an observational, case-control 

study that is subject to the limitations mentioned. The investigators have performed a 

substantial number of sub-analyses to try to understand potential bias and confounding. The 

planned follow-up study will address the limitations mentioned. 

Dr. Karron requested further information regarding the sub-analysis that was matched on LMP 

and all of the problems related to that, and the sub-analysis that assessed ultrasound-confirmed 

pregnancies as a subset in terms of future studies. She wondered about the utility of casecontrol studies versus cohort studies, given the difficulty in matching. While she recognized that 

cohort studies are larger and more expensive to conduct, perhaps it would be worth conducting 

further evaluation if there is believed to be a signal. 

Dr. Shimabukuro replied that a sub-analysis was performed which was restricted to those cases 

with fetal cardiac activity. The result was that the odds ratios were still elevated. As mentioned 

in the methods, the SABs were from 5 to less than 20 weeks. That was also restricted to 7 to 

less than 20 weeks, and there was still an elevated odds ratio. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Donahue added that for the sub-analysis in which the study population was restricted to 

women who had an ultrasound in which fetal heart activity was detected, the question on the 

abstraction form was, “Is this a viable pregnancy?” The instructions to the reviewers were to 

look for fetal cardiac activity. Approximately 30% of the total cases reported fetal heart activity. 

As mentioned, it was not possible to repeat the analysis for effect modification because the 

numbers were not sufficient to do so. For the main effects model, the odds ratio actually 

increased. In respect to the study designs, there are some variations on the case-control 

design that might be beneficial in terms of offering some ability to control for individual factors. 

He agreed that the cohort design would be great, except that these do tend to be large, 

expensive, and subject to certain biases. One bias of major concern is the cases of miscarriage 

that occur that are not identified. There may be some association between the unidentified 

cases and the potential that they are more likely not to be vaccinated. Of course, any study 

conducted in a medical setting such as this is going to be subject to that type of bias. 

Regarding the seizure study, Dr. Decker (Sanofi Pasteur) asked whether consideration had 

been given to an entry criterion of receipt of PCV, so that the entire population received PCV 

with or without another vaccine, which might or might not be IIV. He wondered whether an 

association was found with IIV that was, in effect, a modifier for the risk of seizure associated 

with PCV receipt. Or, if this was purely a situation in which because they were assessing IIV 

and some individuals received PCV and that causes seizures, there was an association with 

IIV. That is, is this like drunk driving after rum and Coke, where the Coke has little to do with it? 

Dr. Shimabukuro responded that this is an RCA, so there is sequential monitoring during the 

influenza season. The particular methodology used was based on what was done during the 

2010-2011 influenza season, during which they were assessing IIV and happened to have 

PCV13 surveillance underway at the same time. Thus, they were able to incorporate PCV13. 

The study was focused on IIV3 as the primary vaccine, along with other vaccines as well. He 

acknowledged that Dr. Decker’s point was well-taken. 

Dr. Frank DeStefano (ISO/CDC) said he thought ACIP had seen some data related to this about 

a year previously, which was presented by Jonathan Duffy. These analyses suggested that 

PCV vaccines had an independent effect which became stronger if they were concomitantly 

administered with IIV. 

Dr. Gorman (NIH) pointed out that as CDC becomes increasingly proficient and allencompassing with its surveillance, the numbers surveilled will be larger. Therefore, smaller 

and smaller differences will become statistically significant, making the job for ACIP increasingly 

harder. He recalled a previous presentation on the seizures that could be applied to 

spontaneous abortions as well, in which the number needed to vaccinate (NNV) to see that 

effect was presented. The NNV in a pediatrician’s office presented as a data point would be 

useful in terms of whether they were talking about once a month, once a year, once every 10 

years. Recalling the numbers from the last time the PCV-IIV data were presented, the average 

pediatrician would not see a seizure in his or her entire lifetime. 

Dr. Temte noted that this was similar to the discussion years ago on MMRV, for which the level 

is dramatically similar at about 1 case per 2500. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Ms. Hayes (ACNM/ANA) asked whether Donahue et al. stratified the data based on when the 

vaccine was administered and when the loss occurred, emphasizing that a loss in pregnancy 

after 14 weeks usually has different causes. Between 14 and 20 weeks, there would be 

different risk factors than between 0 and 14 weeks of gestational age. 

Dr. Donahue replied that they did not stratify because very few losses occurred beyond 13 

weeks. The median gestational age for cases in this study was 7 and the peak was right 

around 7. There were not enough cases beyond 13 weeks to stratify the analysis. 

It was not clear to Dr. Sawyer (PIDS) what practitioners should do regarding the statement on 

influenza vaccine and seizures. Under moderate problems reported, the advice is to “Tell your 

doctor if a child who is getting an influenza vaccine has ever had a seizure.” Practitioners do 

not counsel to give separate vaccines or antipyretics. 

Dr. Shimabukuro replied that what is placed on the VIS and the counseling that physicians offer 

are outside of the realm of the Immunization Safety Office (ISO). 

Dr. Ault (ACOG) emphasized that many women in the case group were vaccinated within days 

of a missed period. Many women do not realize they are pregnant during this timeframe. 

Women who are vaccinated very early bias the study toward a low-risk group of controls and a 

high-risk group of subjects. He thought this explained most of the findings of this study. 

Dr. Baker (IDSA) emphasized that little progress has been made with influenza vaccines in 

pregnant women since the pandemic, which relates to historical concerns. Now there are these 

data, with their limitations. She asked CDC’s view and communication efforts regarding 

vaccination of women during the first trimester. 

Dr. Schuchat replied that the pre-ACIP review of these data suggested that there was no need 

to change communication about influenza vaccine. This session’s discussion was intended to 

focus on whether the signal merited further study for validation. A number of good comments 

were made regarding concerns about the validity of the study, which will inform the research 

plans. The limitations already raised suggested that the messages about influenza 

immunization during pregnancy do not need to be changed at this time. CDC has periodically 

revisited communication in the VIS rereading seizures relevant to influenza, MMRV, and 

PCV13. That will continue to be reviewed to ensure that the information is consistent and is 

communicated clearly for clinicians and consumers. 

Recognizing that it might be a problem with small numbers, Dr. Temte asked whether any 

difference was observed when monovalent administration was followed by trivalent. 

Dr. Shimabukuro responded that there was an effect modification for both seasons, so receipt 

of a monovalent over a trivalent was significant. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

High-Dose Influenza Vaccine Update 

Lisa A. Grohskopf, MD, MPH

Influenza Division 

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention 

Dr. Grohskopf noted that as mentioned earlier in this session, the WG has had a number of 

discussions over the last several months regarding the use of high-dose and standard-dose 

influenza vaccines for older adults. While this is an ongoing discussion, the WG wanted to 

provide an update and invite comments from ACIP regarding how to proceed further. 

In terms of background, high-dose inactivated influenza vaccine (HD-IIV) is only available as 

Fluzone® High-Dose from Sanofi Pasteur. It was approved in 2009. The basis for approval was 

superior immunogenicity compared with standard-dose inactivated influenza vaccine (SD-IIV) 

for persons greater than or equal to 65 years of age. A large randomized-controlled 

comparative trial was conducted over the 2011-2012 and 2012-2013 influenza seasons, which 

demonstrated a 24.2% better relative efficacy of HD-IIV versus SD-IIV for the prevention of 

laboratory-confirmed influenza associated with a protocol-defined influenza-like illness (ILI) 

among persons 65 years and older [DiazGranados CA, et al, N Engl J Med 2014; 371: 635-45]. 

Current ACIP recommendations state that either HD-IIV versus SD-IIV is an appropriate option 

for persons of this age group. 

For this evaluation, the question assessed was: “Do benefits and harms favor HD-IIV versus 

SD-IIV for adults 65 years and older (i.e., better efficacy in preventing outcomes of interest; 

comparable safety profile)?” The population was adults 65 years of age and older. The 

intervention group was HD-IIV and the comparison group was SD-IIV. Because two vaccines 

were being compared head-to-head, the evaluation focused on head-to-head trials and 

abstracting data on each vaccine rather than placebo-controlled trials of one vaccine or 

another. Potential effectiveness and safety outcomes were generated by the influenza WG. 

Safety outcomes were further discussed with members of the Clinical Immunization Safety 

Assessment (CISA) Project for their input, and were ultimately rated in terms of perceived 

importance to policy-making decisions using a 1 to 9 scale, with 7 to 9 being critical, 4 to 6 

being important, and 1 to 3 being considered not important for policy-making decisions. This 

was a somewhat more complicated analysis than was performed for LAIV, largely due to the 

fact that too many outcomes were included because several outcomes were interesting and 

relevant. 

Regarding the efficacy analysis, the critical outcomes focused largely on laboratory-confirmed 

influenza (LCI) outcomes. For the purpose of the analyses, LCI meant that culture or PCR was 

used to confirm infection. The outcomes included any LCI from any virus or subtype, LCIassociated hospitalization, LCI-associated pneumonia, medically attended LCI or visits due to 

LCI, and LCI-associated emergency department visits. Important outcomes included medically 

attended acute respiratory illness (MAARI) and any ILI without regard to culture confirmation of 

the etiology. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Reviewing the literature for potential sources of efficacy and effectiveness data, five RCTs and 

one observational study were found. Further reviewing these studies, two papers were found 

that addressed the outcomes of interest: 1) DiazGranados 2014, which was a very large study 

of over 30,000 enrollees; and 2) DiazGranados 2013, which was the precursor of the 2014 

study. The 2013 study was a very similar design, was initiated during the 2009-2010 season, 

and was intended to be a multi-year study. But the pandemic came about during 2009, which 

made it difficult to assess seasonal influenza vaccine VE. Therefore, the 2013 study was 

stopped and a similar study began again, which became DiazGranados 2014. Of note, there 

was no information for a number of outcomes that were also considered either critical or 

important. No studies addressed LCI-associated deaths or a number of other important 

outcomes focused primarily on the impact of influenza on independence and the ability to 

maintain activities of daily living among the elderly. 

In terms of efficacy outcomes, there was a significant difference favoring HD-IIV. The critical 

outcome of LCI (all viral types and subtypes) was assessed two ways. Both analyses used 

DiazGranados 2013 and 2014 reported LCI influenza outcomes. Because DiazGranados 2013 

occurred at the beginning of the pandemic, it might be argued that it is not fair to include it. It 

could be anticipated that a seasonal vaccine would not cover a relatively antigenically novel 

pandemic strain. When both RCTs were included in the analysis and no parameters were 

downgraded, the overall evidence was Type 1 (high) with a risk difference of 0.82 and a 95% 

confidence interval of 0.71 to 0.95. When DiazGranados 2013 was removed, those numbers 

remained the same. The risk difference changed very slightly. In the assessment for the 

individual studies, the weight of DiazGranados 2013 was lower. It was a smaller study with 

fewer overall events reported. At least in analyzing in this manner, the risk ratio and confidence 

interval were similar regardless of whether DiazGranados 2013 was included. 

For the other critical outcomes (LCI-associated hospitalizations, LCI-associated pneumonia, 

medically attended LCI, and LCI-associated emergency department visits), the only data 

available were from DiazGranados 2014 that were reported in the supplementary material 

published with the New England Journal of Medicine (NEJM) article. This analysis was 

downgraded for indirectness, given that the events were reported as any such event that 

occurred within a 30-day period after the LCI. Particularly for hospitalization and emergency 

department (ED) visits within this age group, the WG considered the possibility that these 

diagnoses or events were not necessarily related to influenza or the index illness at that time 

period. This analysis was also downgraded for imprecision, given that the confidence intervals 

were fairly wide and that the criteria were met in only three out of four cases. Only medically 

attended LCI was not downgraded for imprecision. The overall evidence types were Type 3 

(low) for hospitalization, pneumonia, and ED visits; and Type 2 (moderate) for medically 

attended or medical visits due to LCI. In no case was the difference significant. 

Critical safety outcomes included AE causing study discontinuation and any related SAE. 

Important outcomes included any SAE, any death, fever (any grade), myalgia (grade ≥2), 

headache (grade ≥2), malaise or fatigue (grade ≥2), local swelling/induration (grade ≥2), and 

local pain (grade ≥2). For this analysis, there were more data sources for most of the 

outcomes. In a review of literature, 7 RCTs were found that provided some degree of safety 

data. The important outcomes of fever, myalgia, headache, malaise or fatigue, local swelling / 

induration, and pain were largely reported by two studies: Couch 2007 and Falsey 2009. 

Falsey is regarded as the pivotal safety study for HD-IIV versus SD-IIV. Symptomatic AEs were 

reported by Keitel 2006, although some of them were reported in a way that made abstracting 

the individual symptoms difficult. The WG will return to this when this assessment is performed 

again. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

For the critical safety outcomes (AE causing study discontinuation, any related SAE, and 

immediate hypersensitivity or anaphylaxis), some studies reported an event count of 0 and did 

not contribute to risk calculations. Immediate hypersensitivity / anaphylaxis was not reported for 

any study. AE causing study discontinuation and any related SAE were downgraded for 

imprecision because the 95% confidence interval included 1.0 and exceeded 0.75 in the lower 

bound and/or 1.25 in the upper bound, for an overall quality of evidence of Type 2 (moderate). 

There was no significant difference between AE causing study discontinuation or any related 

SAE between the two vaccine groups. There was a significant amount of discussion with the 

CISA Project and the WG regarding immediate hypersensitivity or anaphylaxis. There was 

general consensus that had these events occurred, they would have been reported. Assuming 

that was the case, there would have been zeros in all cells and none of the parameters could 

have been calculated for risk difference or relative risk. While it may be possible to acquire 

more information in the future, this is about as much as can be said at this time. 

As originally conceptualized, deaths were not stratified by time. However, because some of the 

papers stratified in this way, the decision was made to divide the important safety outcomes into 

three groups (any SAE without regard to relatedness, any death within 6 months, or any death 

within 30 days) and present the results this way. Death within six months was downgraded for 

an imprecise / wide confidence interval. Any death within 30 days with an extremely wide 

confidence interval was downgraded, and the outcome of any SAE was not downgraded. 

Unfortunately, any SAE is a general outcome and it was not possible to confirm whether those 

were due to influenza. Most likely, they were not. In many trials, SAEs are not due to the 

intervention. However, it was one of the few interventions with which they could try to capture 

potentially bad events that may be associated. There were 7 studies that contributed to this 

analysis. The overall evidence was Type 1 (high) for any SAE, Type 2 (moderate) for death 

within 6 months, Type 3 (low) and for death within 30 days. In any condition for all three of 

these, there were no significant differences in the pooled relative risk between the two vaccines. 

No significant difference was observed for the important outcomes of fever of any grade or 

myalgia >2. Only imprecision was downgraded, for an overall evidence of Type 2 (moderate). 

There was a significant difference in moderate to severe headache and moderate to severe 

malaise or fatigue, both on the order of a relative risk of about 1.5. No features were 

downgraded for these outcomes, and the overall evidence was Type 1 (high). Each of these 

outcomes was addressed by Falsey et al. (the pivotal safety study mentioned earlier) and the 

smaller Couch study. Anecdotally, the grade 3 only observations were also considered for each 

of these outcomes and observed a strong association for myalgia and a slightly stronger 

association for the other two outcomes. However, doing so eliminates Couch and leaves only 

one study from one season. 

In terms of the important outcome of local swelling or induration of grade ≥2, a significant 

difference was observed in local swelling or induration and no parameters were downgraded. 

Both studies addressed this outcome. A significant difference was not observed for local pain 

or tenderness of grade ≥2. This outcome was downgraded for the wide confidence interval. 

The overall evidence was Type 2 (moderate). 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Event counts for Couch 2007 were fewer, so that study was weighted less. When the analyses 

were restricted to grade 3 events only, Couch generally had zero events in each cell and fell 

out. It was not that Couch did not report these events. It was just that the events did not occur. 

This resulted in a pooled relative risk, which was really a pool of one study. Similarly, for 

malaise or fatigue of grade 2 or higher for which there was a significant difference of 1.5, Couch 

reported some symptoms. Local swelling or induration with a pooled ratio of 1.6 was also 

significant. 

To summarize critical outcome results, there was a difference that favored high-dose vaccine 

for prevention of laboratory-confirmed influenza with high quality evidence. There was no 

difference and low to moderate quality evidence in the findings for the efficacy / effectiveness 

outcomes of LCI-associated hospitalization, LCI-associated pneumonia, medically attended 

LCI, or LCI-associated ED visits; or the safety outcomes of SAEs causing study discontinuation 

or any related SAE. There is no information on deaths. The overall quality of evidence for this 

assessment was deemed to be Type 3 (low). 

There are a number of limitations to this analysis. The main source for efficacy outcomes is a 

single study conducted over two seasons. Having two seasons is good in that influenza varies 

from season-to-season in terms of vaccine effectiveness and reactogenicity. Outcomes could 

be impacted as well by not having more than one season represented. Data were not available 

for a number of critical outcomes (LCI-associated deaths, anaphylaxis), or available data were 

indirect (LCI-associated severe clinical outcomes). However, it is potentially difficult to power a 

RCT for these outcomes. Hospitalizations may be difficult as well, possibly requiring a large 

observational study. Some of the safety outcomes of interest are very uncommon, again 

making it difficult to power for some of these outcomes. In addition, safety outcomes may not 

have been defined or interpreted similarly across studies. Though fever was defined relatively 

uniformly, swelling was not. This resulted in the need to make some assumptions. 

It is important to note that an additional study was found but not included in the GRADE 

analyses [Izurieta HS, et al, Lancet Infect Dis, online February 9, 2015]. This was a 

retrospective cohort study of Medicare beneficiaries 65 years of age and older who received 

HD-IIV or SD-IIV during the 2012-2013 influenza season. The primary outcome was probable 

influenza infection based on receipt of a rapid influenza test followed by dispensing of 

oseltamivir. The secondary outcome was a hospital or ED visit listing a Medicare billing code 

for influenza. Among 929,730 HD-IIV recipients and 1,615,545 SD-IIV recipients identified, HDIIV was 22% (95%CI 15-29) more effective in preventing probable influenza; and 22% (95%CI 

16-27) more effective in preventing influenza hospital admission. However, this study was not 

included in GRADE it did not address critical / important outcomes selected by the WG, and that 

it would have been somewhat of a stretch to call this LCI. As an observational study, it would 

have started out as Type 3 evidence, which already would have been low. The study likely 

would have had to be downgraded simply because, at minimum, it did not address a direct 

outcome. 

Also important to note is that VAERS is constantly collecting safety data. A paper was 

published by Moro et al. based on VAERS data for the 2010-2011 influenza season, which 

analyzed events associated with HD-IIV. There were 606 reports in patients 65 years of age or 

older. Only 8.2% of these events were judged as serious, which is reassuring. MedDRA terms 

for ocular hyperemia and vomiting exceeded the data-mining threshold during that period. Of 

these reports, 80% were non-serious, which also is reassuring. Clinical review of serious 

reports found a greater proportion of gastrointestinal events compared to IIV3 standard dose. 

During the first year after US licensure of trivalent, inactivated influenza vaccine (TIV-HD), no 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

new serious safety concerns were identified in VAERS. Analyses suggested a clinically 

important imbalance between the reported and expected number of gastrointestinal events after 

IIV3-HD receipt [Moro et al. Postlicensure safety surveillance for high-dose trivalent inactivated 

influenza vaccine in the Vaccine Adverse Event Reporting System, 1 July 2010-31 December 

2010. Clin Infect Dis. 2012;54(11):1608-14]. 

Regarding Fluzone High-Dose® post-licensure safety data from 2011-2015, between 2011 and 

2015 disproportional reporting for the MedDRA term “vomiting” was observed during the 2012 

and 2013 season. Most vomiting reports were non-serious and self-limited. There also was 

disproportional reporting for the MedDRA term “drug administered to patient of inappropriate 

age,” which is more of an error than an AE. No new safety concerns were identified in VAERS 

reporting for Fluzone High-Dose® in monitoring from 2011-2015 following its initial season of 

use. 

The WG does have a continuing interest in populations who are vulnerable to more severe 

outcomes. However, the WG does not think there is consensus at this time that alternative 

policy language or preferential language should be proposed based on the available evidence. 

The WG will consider further evaluation as more data become available. They are aware of at 

least one other study that is being conducted currently in elderly nursing home patients, for 

which the data are not anticipated to be available for at least another year. 

Discussion Points 

Dr. Greenberg (Sanofi Pasteur) noted that Sanofi Pasteur looks forward to ongoing discussions. 

They have been performing more analyses on the data available from the seminal trial. He 

agreed with the conclusion that it did not make sense to include the data from the 2009-2010 

season in GRADE since the strain was not in either HD-IIV or SD-IIV. Regarding the primary 

study, he noted that the 24.2% relative efficacy reduction of disease noted in this presentation 

was the primary endpoint of the study. Based on the presentation, it appeared that relative 

efficacy for any laboratory-confirmed respiratory illness was used. That was a less sensitive or 

less severe case in the sense that respiratory illness of that study was defined as “any one 

respiratory symptom.” Sneezing alone would qualify for a respiratory infection; whereas, the 

protocol-defined ILI was at least one systemic symptom and one respiratory symptom. 

Publications are anticipated in the summer and fall that pertain to some of the secondary 

analyses and cost-effectiveness. Sanofi Pasteur looks forward to sharing those data with the 

WG. At 24% relative efficacy, there is a substantial cost savings because of reduced influenzarelated hospitalizations. He thinks that is an important or critical endpoint the WG will want to 

consider. 

Dr. Grohskopf replied that the WG did use the respiratory illness definition in the hope of 

capturing as large a number of cases as possible. They did consider the other definitions as 

well, because that paper lays out the results for the different definitions of respiratory illness 

used. 

Dr. Decker (Sanofi Pasteur) reminded everyone that influenza-related deaths in the over-65 

population is 1% annually. Therefore, anything that might be influenza-specific is swamped by 

other numbers. That is why it is very difficult to exact anything at all for that particular 

parameter. Regarding the Izurieta study, he recognized that GRADE has rules and that the 

study is observational, is not laboratory-confirmed, et cetera. However, this is a major CDC / 

FDA / CMS study with over 2 million subjects evaluated. A primary outcome of this study was a 

22% statistically significant reduction in the rate of hospitalization. To say, “Well, it’s outside of 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

our rules” when it is CDC’s own study seemed a little strange. He noted that the nursing home 

study is also observational, so while waiting for it, they should review Izurieta again. 

Dr. Grohskopf emphasized that there is absolutely no prohibition against using observational 

studies, and they would like to see more of them. In fact, observational data were used in the 

last assessment of LAIV vs IIV for young children. It was more an issue of trying to walk the 

balance between what are believed to be the most important outcomes. In the past, there has 

been a lot of discussion regarding the use of more specific outcomes for influenza vaccine. For 

example, rather than using serologic data, perhaps using hard endpoints associated with labconfirmed disease. CDC and the WG believe the Izurieta study to be important, which is why 

they raised it for discussion. It did not quite fit within GRADE. Had it been used in the GRADE 

analysis, it probably would have lowered the quality of evidence because they would have to 

have downgraded it. They would like to include more observational studies, and will continue to 

search for them. 

Proposed Recommendations 

Lisa A. Grohskopf, MD, MPH

Influenza Division 

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention 

Dr. Grohskopf first recapped what occurred during the truncated February 2015 ACIP meeting. 

As is typical in February of each year, the core guidance was reiterated that annual, routine 

influenza vaccination is recommended for all persons aged 6 months and older. That was 

approved and was signed off on the Internal Decision Memo, as was the revision of the 

recommendations regarding use of LAIV for healthy children 2 through 8 years of age and that 

for the next season, no preference is expressed for LAIV or IIV for any person aged 2 through 

49 years for whom either vaccine is otherwise appropriate. Further proposed updates for 2015­

2016 included the US influenza vaccine composition for 2015-2016 (there are a couple of strain 

changes, so that will be mentioned); updated influenza vaccine product descriptions, reflecting 

new licensures, labeling information, and expected availability; and a revised algorithm for 

determining the number of doses needed for children 6 months through 8 years of age. 

For information and not a vote, there is a strain change in the vaccine composition for 2015­

2016. The H1N1 virus will be the same A/California/7/2009-like virus, which is the 

(H1N1)pdm09 type virus. That has been in the seasonal vaccine since 2010-2011. There will 

be a new H3N2 strain, A/Switzerland/9715293/2013 (H3N2)-like, which replaces 

A/Texas/50/2012-like viruses. For B strains, the B/Phuket/3073/2013-like virus, which is a 

Yamagata lineage virus, will replace the B/Massachusetts/2/2012-like virus, which is a different 

Yamagata lineage virus. For the quadrivalent vaccines, these viruses will be present plus a 

B/Brisbane/60/2008-like virus (Victoria lineage). That was also the second B virus 

recommended for last season, so that is not a change. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

New licensures, labeling information, and expected presentations reflected in text and/or table 

for influenza vaccine product updates for 2015-2016 will include the following: 

 Fluzone® Intradermal Quadrivalent IIV 

 Expanded age indication for Flublok® (now 18 and older), which was previously noted in the 

online vaccine table and the ACIP Adult Schedule 

 Approval of administration of Afluria® by Stratis® jet injector for persons 18 through 64 years 

of age, which was previously noted in the online vaccine table 

 Any additional labeling changes arising prior to publication 

Regarding determination of doses needed for children months through 8 years of age, since 

2010-2011, the algorithm for determining the appropriate number of doses in this age group has 

considered vaccine doses containing A(H1N1)pdm09 separately. As a pandemic virus, it is 

considered to be relatively antigenically novel. This led to somewhat complicated algorithms. 

This virus has been represented by an A/California/7/2009 (H1N1)-like virus in trivalent and 

quadrivalent vaccines since 2010-2011. There is likely a diminishing number of children each 

season who have not been exposed to this virus. The WG proposed language that would 

eliminate separate counting of doses containing A(H1N1)pdm09-type virus in order to have a 

single simplified algorithm as depicted in the following graphic: 

Discussion Points 

Dr. Schuchat asked whether “tri” or “quad” could be crossed out. 

Dr. Grohskopf replied that “trivalent” and “quadrivalent” were included so that monovalent 

vaccine doses would not be counted as one of the two previous doses. If a child received one 

dose of seasonal and one dose of monovalent pandemic vaccine, that child should receive two 

doses. 

Dr. Kimberlin (AAP) said he personally liked having trivalent or quadrivalent simply because 

practitioners will think about it. 

Dr. Kempe asked if the WG discussed clarifying that it need not be concurrent seasons, given 

the potential for confusion. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Grohskopf noted that this was the reason for the addition of the footnote, and that the text 

also discusses that the doses do not need to be administered during the same season. She 

suggested stating that “The two doses do not need to have been received during the same 

season or consecutive seasons.” 

Dr. Belongia suggested asking “Has the child previously received two or more total doses of 

trivalent or quadrivalent influenza vaccine?” and keeping the footnote. 

Dr. Hahn (CTSE) expressed concern regarding removing the wording about prior seasons. A 

child who already received an influenza vaccine in that season may still be interpreted as 

needing another dose. She suggested removing the word “any” since it made it seem like only 

one season and asking, “Has a child received two or more total doses during prior seasons?” 

Dr. Grohskopf said the more she thought about it, what made the most sense was to remove 

“any prior seasons” to have the question read “Has the child previously received two or more 

total doses of trivalent or quadrivalent influenza vaccine?” and add to the footnote that they do 

not have to have been in consecutive seasons. 

Dr. Loehr (AAFP) pointed out that one problem would be if someone received a dose in 

September 2015 as well as during the previous year, and thought they did not need another 

dose in October. 

Dr. Grohskopf acknowledged that this would be counting across the current upcoming season 

and the last season. She suggested that a simple fix might be in the last two boxes where the 

number of doses are specified to state “of 2015-2016 influenza vaccine” to specify the current 

season. She clarified that the language would be “Has the child previously received two or 

more total doses of quadrivalent or trivalent influenza vaccine? If yes, one dose of 2015-2016 

influenza vaccine. If no or don’t know, two doses of 2015-2016 influenza vaccine.” The 

footnote would be amended to state, “The two doses need not have been received during the 

same season or consecutive seasons.” 

Dr. Temte clarified that the motion and vote would be for the language change proposed for the 

2015-2016 influenza season recommendation for the number of doses for children 6 months 

through 8 years of age and to affirm the vaccine components and product updates. 

Vote: 2015-2016 Influenza Season Recommendation Language 

Revision for Number of Doses for Children 6 Months through 8 Years of Age 

and Affirmation of Vaccine Components and Product Updates 

Dr. Kempe made a motion to for the language revision proposed to the recommendation for the 

doses needed for children 6 months through 8 years of age for the 2015-2016 influenza 

season, and to affirm the components of the 2015-2016 vaccine components and product 

updates. Ms. Pellegrini seconded the motion. The motion carried with 14 affirmative votes, 0 

negative votes, and 1 abstention. The disposition of the vote was as follows: 

14 Favored: Bennett, Bocchini, Campos-Outcalt, Harriman, Harrison, Karron, Kempe, 

Pellegrini, Romero, Reingold, Riley, Rubin, Temte, and Vazquez 

0 Opposed: N/A 

1 Abstained: Belongia 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Smallpox Vaccine 

Introduction 

Lee Harrison, MD 

ACIP, Work Group Chair 

Dr. Harrison reminded everyone that numerous occurences of laboratory-acquired 

orthopoxviruses infections have been reported. The current smallpox vaccine provides crossprotection against all orthopoxviruses that cause infections in humans (e.g., smallpox, 

monkeypox, vaccinia, and cowpox). Smallpox vaccine is currently used to protect clinical and 

research laboratory workers against these viruses. He shared several images of ocular, ear, 

and needlestick vaccinia virus transmissions in laboratory workers and smallpox vaccination 

complications. The types of complications shown generally do not occur with the type of 

screening currently utilized to exclude persons with contraindications prior to immunization. 

Regarding vaccination versus laboratory infections, with vaccination there is a well-formulated 

virus in a dosage delivered through a controlled route at a location that minimizes risk of 

spread. In terms of laboratory infection, a variety of strains are being used with unknown 

pathogenic potential, there may be high titers of virus, and transmission may occur through an 

unusual route (e.g., deep injection, atypical site on body, ocular exposure) [Source: Mary 

Reynolds]. 

In terms of background, ACIP recommendations for smallpox vaccination of laboratory workers 

have not been updated since 2003. A new smallpox vaccine, ACAM2000TM, was licensed in 

2007 and has replaced the previously used smallpox vaccine, Dryvax®. The Smallpox Vaccine 

Work group was established in March 2013, and monthly meetings have been held since that 

time. This has been a very productive group, which has engaged in detailed discussions and 

provided significant input. 

The work group’s terms of reference are as follows: 

1.	 Review recommendations for smallpox vaccination for lab workers in 2001 statement (and 

supplements from 2003): 

a.	 Review Biosafety in Microbiological and Biomedical Laboratories (BMBL) 

requirements for work with orthopoxviruses 

b.	 Review orthopoxvirus laboratory exposure cases and reports 

2.	 Review data on smallpox vaccine: 

a.	 ACAM2000TM 

•	 Safety and immunogenicity data 

•	 Adverse event rates with current stringent prescreening program 

b.	 Dryvax: Publications on 2002 through 2004 pre-event smallpox vaccination program 

3.	 Review human safety and animal model efficacy data for attenuated smallpox vaccine 

IMVAMUNE stored in Strategic National Stockpile and potential role in smallpox vaccination 

for lab workers (unlicensed product and therefore informational). 

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4.	 Review data on recombinant vaccinia viruses in development or under investigation in 

clinical trials to provide guidance on need for smallpox vaccination in healthcare and/or 

laboratory personnel working with these viruses. 

5.	 Revise existing statement and supplements for smallpox vaccination of laboratory workers 

into single ACIP Policy Note document. 

Proposed Smallpox Vaccine Recommendations 

Brett W. Petersen, MD, MPH 

Medical Officer, Poxvirus and Rabies Branch, CDC 

Lieutenant Commander, U.S. Public Health Service 

Dr. Petersen indicated that with regard to background, orthopoxviruses are a group of large 

double-stranded DNA viruses within the family Poxviridae. There are four known species that 

infect humans: Variola (Smallpox), Vaccinia (Smallpox Vaccine), Monkeypox, and Cowpox. 

Orthopoxvirus virus infections provide cross-protection across species. It is this property that 

allowed the development of vaccinia as a vaccine for smallpox and other orthopoxviruses and 

has ultimately resulted in eradication of smallpox as a human disease. However, 

orthopoxviruses remain an active subject of research. 

In particular, vaccinia viruses are commonly used in laboratory research. There are many 

historic vaccine seed stocks and derivatives including the following: New York City Board of 

Health (NYCBH), Lister, Modified Vaccinia Ankara (MVA), Western Reserve, LC16M8, 

Copenhagen, among others. Different vaccinia viruses demonstrated varying degrees of 

attenuation and safety profiles. Recombinant vaccinia viruses are being used increasingly in 

the laboratory setting as viral vectors for expression of foreign genes using gene therapy or 

genetic engineering, and are also under investigation as potential recombinant vaccines and as 

oncolytic or immunotherapy for cancer. 

Vaccinia virus smallpox vaccines have been recommended by ACIP for the protection of 

laboratory workers against orthopoxvirus disease since 1980. ACIP last produced 

recommendations for vaccinia vaccine for laboratory workers in 2001. At that time, ACIP 

recommended vaccinia vaccine for laboratory workers who directly handle cultures or animals 

contaminated or infected with non-highly attenuated vaccinia virus, recombinant vaccinia 

viruses derived from non-highly attenuated vaccinia strains, or other orthopoxviruses that infect 

humans (e.g., monkeypox, cowpox, vaccinia, and variola). Vaccination can be offered to 

healthcare workers with direct contact with dressings or other infectious material from 

volunteers in clinical studies where non-highly attenuated vaccinia viruses or recombinant 

viruses derived from these strains are used. Laboratory and healthcare personnel working with 

highly attenuated poxvirus strains do not require routine vaccinia vaccination. Highly 

attenuated poxvirus strains include the following: 

 MVA: Derived from vaccinia virus Ankara 

 NYVAC: Derived from vaccinia virus Copenhagen 

 TROVAC: Derived from fowlpox virus 

 ALVAC: Derived from canarypox virus 

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ACAM2000TM is currently the only smallpox vaccine licensed and available in the US. It was 

licensed in 2007 and replaced the previously used smallpox vaccine, Dryvax, which was 

referred to in the previous ACIP recommendations and is no longer available. ACAM2000TM 

has been used in laboratory and healthcare workers and select DoD personnel. It is a live 

vaccinia virus vaccine that is produced in vero cells. It is derived from a clonal isolate of 

Dryvax, a New York City Board of Health strain used during the smallpox eradication campaign. 

ACAM2000TM is administered in a single dose percutaneously via multiple puncture with a 

bifurcated needle. Following vaccine administration, a lesion develops at the site of 

vaccination. During this time, the lesion does contain infectious virus that can be transmitted to 

others via inadvertent inoculation or to other sites of the body via auto-inoculation. However, 

this cutaneous response is also referred to as a “take” and is considered a marker of successful 

vaccination. 

Historically, smallpox vaccines have been associated with a number of adverse events, some of 

which can be severe and life-threatening. Some of those include eczema vaccinatum, 

progressive vaccinia, and postvaccinial encephalitis. Based on data from primary vaccination 

with Dryvax® from a study conducted in 1968 during the time of routine immunization with 

smallpox vaccine, the rates ranged from 1.5 cases/million vaccinations to 38.5 cases/million 

vaccinations. Overall rates for deaths were also reported as approximately 1 death/million 

vaccinations. The rates for revaccination were much lower than those for primary vaccination 

[Adapted from Lane JM, Ruben FL, Neff JM, Millar JD. Complications of smallpox vaccination, 

1968: results of ten statewide surveys, J Infect Dis. 1970 Oct;122(4):303-9 and ACAM2000TM 

package insert]. 

Based on data from a more recent study evaluating the adverse event rates observed during 

the DoD and HHS vaccination programs during 2002 and 2005, of note was the absence of any 

observed eczema vaccinatum or progressive vaccinia cases. This was likely due to the 

stringent screening of persons for risk factors for these adverse events. Also of note was the 

identification of myo/pericarditis, which had not previously been recognized as a significant 

adverse event related to smallpox vaccine [Adapted from Poland GA, Grabenstein JD, Neff JM. 

The US smallpox vaccination program: a review of a large modern era smallpox vaccination 

implementation program. Vaccine 2005, Mar 18;23(17-18):2078-81 and ACAM2000TM package 

insert]. 

Using this background, the WG used the GRADE methodology to assess the ACAM2000TM in 

laboratory workers utilizing the following steps: 

 Development of a policy question 

 Identification and assessment of the importance of outcomes 

 Review of the literature 

 Summarization of the evidence for critical outcomes 

 Evaluation of the quality of evidence for outcomes 

The policy question formulated by the WG was, “Should administration of ACAM2000TM be 

recommended routinely to persons at risk for occupational exposure to orthopoxviruses?” The 

population of interest was persons at risk for exposure to orthopoxviruses. The intervention 

was vaccination with ACAM2000TM, the currently available vaccine, and the comparison was 

vaccination with the previously recommended vaccine, Dryvax. A modified Delphi method was 

used to solicit outcomes assessments from the WG members. The outcomes identified 

included benefits and harms. Among the benefits were vaccine efficacy to prevent 

orthopoxviral disease, cutaneous response or take, and neutralizing antibody response. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Among the harms were serious adverse events, myo/pericarditis resolved with sequelae, 

myo/pericarditis resolved without sequelae, inadvertent inoculation, and mild adverse events. 

Outcomes deemed to be critical were vaccine efficacy to prevent orthopoxviral disease, serious 

adverse events, and myo/pericarditis resolved with sequelae. All of the outcomes were 

assessed to be important and all were eventually included in the final evidence profile. 

A systematic literature review was performed to identify studies that met the criteria and 

addressed the outcomes identified by the work group. A total of 5 RCTs were identified that 

addressed the benefits outcomes, 4 of which also addressed the harms outcomes. Cutaneous 

response was best assessed in two studies evaluating this outcome in vaccinia-naïve and 

previously vaccinated subjects who were vaccinated with both ACAM2000TM and the 

comparator Dryvax. Of vaccinia-naïve subjects receiving ACAM2000TM, 96% demonstrated 

vaccination success. ACAM2000TM was found to be non-inferior to the comparator, Dryvax, 

among this population. Of the previously vaccinated subjects receiving ACAM2000TM, 84% 

demonstrated vaccination success by cutaneous response as compared to 98% of Dryvax® 

subjects. A statistical analysis revealed that ACAM2000TM did not meet the predefined criteria 

for non-inferiority to Dryvax® among this population. In terms of the neutralizing antibody 

response, these same studies evaluated the response in both vaccine-naïve and previously 

vaccinated subjects. Among vaccinia-naïve subjects, the geometric mean neutralizing antibody 

titer and the Log10 mean were comparable to the comparator, Dryvax, although by the slightest 

of margins ACAM2000TM did not meet the criteria for non-inferiority to the comparator vaccine. 

In contrast, among the previously vaccinated subjects, the neutralizing antibody titers were 

again similar and in this instance did meet the criteria for non-inferiority. 

Regarding the critical harms outcomes, no serious adverse events were reported in the RCTs 

reviewed (e.g., death, eczema vaccinatum, progressive vaccinia, or postvaccinial encephalitis). 

There were 7 cases of suspected myo/pericarditis reported among the 2983 clinical trial 

participants who received ACAM2000TM. The best estimate of risk based on detection of 5 

cases among 873 vaccinees during Phase 3 clinical trials incorporating active monitoring for 

myocarditis and pericarditis is 5.7 cases/1000 vaccinees. Two cases among those reporting 

myo/pericarditis demonstrated sequelae (e.g., persistent abnormal echocardiogram at one 

year). All cases of myo/pericarditis in these clinical trials did resolve. 

Using the GRADE methodology to assess the evidence, the WG had no concerns for risk of 

bias or inconsistency for any of the outcomes. However, concerns about indirectness and 

imprecision were identified as issues for several outcomes and the evidence type was 

downgraded accordingly. Three outcomes were downgraded for indirectness, because the 

outcome that was assessed differed from those of primary interest. Cutaneous response and 

neutralizing antibody response were used as surrogates for the outcome of primary interest, 

which was vaccine efficacy to prevent orthopoxviral disease. No data were available for this 

primary outcome. The clinical significance of myo/pericarditis, which resolved without sequelae, 

is unclear. Many of these cases were asymptomatic disease that were only detected due to the 

intensive cardiac monitoring that participants underwent, including routine EKGs and cardiac 

enzyme evaluation. For this reason, myo/pericarditis that resolved with sequelae was felt to 

better represent the outcome of primary interest. 

Regarding imprecision, the work group found that the clinical trials were not adequately 

powered to detect serious adverse events (e.g., death, eczema vaccinatum, progressive 

vaccinia, or postvaccinial encephalitis), and were not powered to detect inadvertent inoculation. 

Calculations of the probability that these adverse events would not be observed based on the 

number of participants in the clinical trials, as well as the sample size that would be needed to 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

detect these events, support the assessment of imprecision in these cases. Based on this 

GRADE assessment, the overall level of evidence was determined to be 2, which is consistent 

with RCTs with important limitations. 

The WG also considered the risk of exposure and infection in developing the proposed 

recommendations, and found that these risks are very difficult to quantify. The population at 

risk is difficult to estimate, given that there is no registry of persons who work with 

orthopoxviruses. The WG also assessed indirect measures that offer some sense of the size of 

this population, including the following: 

 431 orthopoxvirus-related publications in 2013 on PubMed (361 with “vaccinia” in title or 

abstract, 34 “monkeypox,” 36 “cowpox”) 

 185 active projects listed on NIH Research Portfolio Online Reporting Tools at 

http://projectreporter.nih.gov/ 

 25 open clinical trials involving vaccinia virus listed on NIH’s clinicaltrials.gov 

 31 different sites received 80 shipments of smallpox vaccine from CDC in 2013 (96 different 

sites received 523 shipments during 2009–2013) 

The risk of orthopoxviral disease is difficult to estimate as well, given that surveillance is not 

ideal and the true burden of disease is not known. Vaccinia and cowpox infections are not 

reportable conditions, so there is not a comprehensive list of all potential infections. Similarly, 

orthopoxvirus exposures are not always reported. In addition, the pathogenicity and virulence 

of the virus may not be well-characterized, particularly with regard to recombinant viruses. 

However, CDC maintains a database of laboratory-related orthopoxvirus exposures and 

infections that have been reported since 2004. Of the 26 exposure incidents reported, 18 

(69%) involved recombinant viruses and 14 (54%) resulted in infections. Of those 14, 12 (86%) 

involved recombinant viruses, 12 (86%) involved vaccinia infections, 2 (14%) involved cowpox 

infections, 4 (29%) required hospitalization, and 4 (29%) involved infection with a strain other 

than that with which they were working (or thought they were working). Of the 26 exposure 

incidents reported, 7 (27%) met ACIP vaccination recommendations, and 1 of those 7 (14%) 

resulted in infection. One other infection occurred in an individual vaccinated over 10 years 

prior, which did not meet the ACIP vaccine recommendations for revaccination. 

In terms of conclusions and recommendations, the WG concluded that ACAM2000TM is 

comparable to Dryvax® in providing protection against orthopoxviruses, with an overall evidence 

Type 2. The WG proposed extending the current ACIP recommendations for use of smallpox 

vaccine among laboratory and healthcare workers at risk for occupational exposure to 

orthopoxviruses. The proposed recommendations presented for a vote follow: 

 Routine vaccination with ACAM2000TM is recommended for laboratory workers who 

directly handle a) cultures or b) animals contaminated or infected with replicationcompetent vaccinia virus, recombinant vaccinia viruses derived from replicationcompetent vaccinia strains, or other orthopoxviruses that infect humans (e.g., 

monkeypox, cowpox, and variola) (recommendation category: A, evidence type 2). 

 Vaccination with ACAM2000TM is not recommended for persons who work only with 

replication-deficient strains of vaccinia virus (e.g., MVA, NYVAC, TROVAC, and ALVAC) 

(recommendation category: A, evidence type 2). 

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 Health-care workers (e.g., physicians and nurses) whose contact with replicationcompetent vaccinia viruses is limited to contaminated materials (e.g., dressings) and 

persons administering ACAM2000TM smallpox vaccine who adhere to appropriate 

infection prevention measures can be offered vaccination with ACAM2000TM 

(recommendation category: B, evidence type 2). 

The WG proposed that contraindications remain in place, with two exceptions: 1) the addition of 

a contraindication for persons with a household contact less than one year of age, given that 

this population is at increased risk of SAEs, particularly postvaccinial encephalitis; and 2) the 

removal of the contraindication for revaccination of persons who have three or more known 

major cardiac risk factors, given that myo/pericarditis was not observed in clinical trial 

participants who were undergoing revaccination and was only seen in primary vaccinees: 

The WG was not unanimous. One WG member submitted the following dissenting view on the 

level of recommendation for workers handling vaccinia virus, as well as alternative language: 

 The risk-benefit ratio for routine smallpox vaccination of laboratory workers handling 

vaccinia virus has changed significantly: 

 As opposed to the ACIP recommendations in 1980, today vaccination of most 

workers is no longer a boost vaccination, but a primary vaccination that carries more 

risk. 

 This change in risk likely should have been addressed in 2001 when the 

recommendations were revised. 

 This change in risk at least needs to be acknowledged. 

 How can the level of evidence and the risk/benefit ratio for lab workers handling vaccinia 

virus be the same as for those working with variola and monkeypox viruses? 

 Variola and monkeypox would cause a more serious infection after a lab accident 

and have public health implications. Thus there is an acceptable risk-benefit ratio 

when recommending routine vaccination for these viruses. 

 The same cannot be said for those working with vaccinia virus. 

 Therefore, the strength of recommendation for all workers handling vaccinia virus needs to 

be adjusted. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Suggested alternative language is as follows: 

 A careful assessment of the type of work being done with vaccinia virus should be made 

and those at high risk of an accidental exposure should be vaccinated. 

 Alternatively, as opposed to “recommendation category: A, evidence type 2” a lower level 

should be assigned to the recommendation to vaccinate workers who handle vaccinia virus: 

 An argument can be made for a lower recommendation category since it is difficult to 

quantify the risk of occupational exposure to vaccinia virus 

There did seem to be general consensus among the WG for a Category A recommendation for 

persons working with vaccinia virus to be vaccinated with ACAM2000TM vaccine. After multiple 

reviews of the language and the Policy Note, Dr. Petersen did not receive any individual input 

from other WG members suggesting that this should be anything other than a Category A 

recommendation. 

Discussion Points 

Dr. Belongia requested additional information about current DoD policy and recent DoD 

experience with the use of ACAM2000TM vaccine, and whether there are any more recent 

safety data from DoD than 2005. 

Dr. Petersen replied that in general, the DoD recommendations and contraindications 

essentially align with ACIP recommendations. The exception would be the proposed changes 

to the ACIP contraindications. In terms of safety data, the WG heard a presentation from the 

DoD that did not identify any new safety signals in the ongoing DoD smallpox vaccination 

program. 

Dr. Campos-Outcalt asked how many members of the DoD are being vaccinated currently. 

Dr. Petersen responded that the DoD is still vaccinating a small number of individuals who are 

being deployed. 

Dr. Sergienko (DoD) added that the DoD is still vaccinating people who are going into areas 

where there is concern for potential high-risk. The safety profile has not changed. 

Dr. Campos-Outcalt observed that the first bullet in slide 26 stated that, “ACAM2000TM is 

comparable to Dryvax® in providing protection against orthopoxviruses (Overall evidence type 

2),” but it was unclear to him how slides 16 and 17 resulted in that statement. 

Dr. Petersen replied that knowing how well ACAM2000TM protects against orthopoxviral disease 

is of interest. Currently, there is little naturally occurring orthopoxviral disease in the world since 

the eradication of smallpox. Showing efficacy for ACAM2000TM in a natural orthopoxvirus 

infection would be difficult. These are surrogates for that outcome, which is of primary interest. 

Cutaneous response has been demonstrated during the smallpox eradication era as a marker 

of vaccination success. Historically, smallpox vaccines were not studied rigorously. There 

were no clinical trials to prove efficacy, but their effectiveness ultimately was demonstrated by 

the eradication of disease. While the WG recognized that these outcomes are surrogates, they 

felt that this offered significant evidence for protection against orthopoxviral disease. 

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Dr. Campos-Outcalt stressed that Dryvax® is no longer an issue in that a choice is not being 

made between ACAM2000TM and Dryvax®. Based on what was shown, ACAM2000TM is not 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Campos-Outcalt emphasized that that differed from the first bullet on Slide 26, which states 

that ACAM2000TM is comparable to Dryvax®. He did not think that Slides 16 and 17 showed 

this to be true. In each instance, there is inferiority to Dryvax® in one of the two groups. He 

was fine with saying ACAM2000TM is believed to be effective, but did not think it was accurate 

to state that it is comparable to Dryvax. 

Dr. Petersen acknowledged that “comparable” is a subjective assessment. Differences were 

demonstrated in these data comparing ACAM2000TM to Dryvax. The arguments to downplay 

the differences would be that in terms of the differences between vaccine-naïve and previously 

vaccinated subjects for ACAM2000TM, it is known that the cutaneous response can be affected 

by previous vaccination. The differences in previously vaccinated subjects may be related to 

that fact, although the numbers are certainly different. With respect to the neutralizing antibody 

response, ACAM2000TM did not meet inferiority to Dryvax®, but a robust neutralizing antibody 

response was observed. The level of antibody response required to provide protection is 

unknown, and it was very close to meeting non-inferiority. 

Dr. Petersen agreed and acknowledged that reasonable people could have differences of 

opinion in terms of language and subjective evaluations. 

Dr. Karron wondered about the laboratory exposure incidents and the fact that only seven 

individuals would have met criteria for vaccination, and whether that was because the other 19 

individuals were working in laboratories or facilities but not working directly with the virus. That 

is, who were those other 19 and why did they not meet criteria? 

Dr. Petersen clarified that the other individuals were not vaccinated at all. Seven met ACIP 

vaccination recommendations, and only one of those actually became ill with the disease. The 

others were exposed, but they were vaccinated according to ACIP recommendations and they 

did not develop orthopoxvirus infection. 

Dr. Schuchat asked whether he meant by “met ACIP vaccination recommendations” that they 

had received the recommended vaccine, and whether all of these people were in a group that 

would have been recommended to receive vaccine. 

Dr. Petersen replied that Dr. Schuchat was correct. 

Dr. Weber (SHEA) said that being at the University of North Carolina where there is a large 

defense group, he has personally taken care of at least two cases from DoD, one with postvaccinia encephalitis and a contact with generalized vaccinia. He has also cared for several 

soldiers who had had recent inoculations, still had dressings, and were in his hospital for other 

reasons. He requested that the word “worker” be changed to “personnel” since he assumed 

graduate students would be working on this as well, and they are not necessarily workers. This 

would make the recommendation more inclusive of students and trainees. He found the 

recommendation for HCP to be much too ambiguous in that it does not provide the precision 

needed. Also, it does not describe who makes the decision to immunize. Is it the facility? It is 

important to keep in mind that vaccine must be acquired from the health department. Is it going 

to be used pre-exposure, such that his hospital should have a group of people who have been 

immunized? Is it going to be used at the time of taking care of a person with a complication of 

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vaccinia? Is it going to be used post-exposure? It doesn’t say anything about boosters. Are 

those people immunized just once, or should they be current within 10 years with a booster? 

He encouraged ACIP to make the recommendation much more precise to give the hospital 

epidemiologist some guidance as to when vaccinia immunization of HCP is indicated. 

Dr. Petersen responded that the WG could attempt to make the language more precise. 

Revaccination is included, but has not changed from previous recommendations so he did not 

make it a point to discuss that. Regarding how the vaccine would be used, this is a very 

specific document targeting a very specific population—persons occupationally exposed to 

orthopoxviruses. It does not involve persons who may be vaccinated for other reasons. 

Certainly, DoD makes their own decisions about smallpox vaccination. The recommendation 

also does not address the potential first responder population. The WG tried to make the 

recommendation as focused as possible specifically on the laboratory personnel population. 

Dr. Weber (SHEA) asked for clarification regarding exactly what HCP the WG was talking about 

in the recommendation—people conducting research or people at a healthcare facility providing 

care to people who have developed complications from vaccinia? 

Dr. Petersen clarified that the recommendation addresses both of those populations. The 

laboratory personnel under these proposed recommendations would be recommended to 

receive smallpox vaccination. The HCW are as described in the proposed language, “healthcare workers (e.g., physicians and nurses) whose contact with replication-competent vaccinia 

viruses is limited to contaminated materials (e.g., dressings) and persons administering 

ACAM2000TM smallpox vaccine who adhere to appropriate infection prevention measures can 

be offered vaccination with ACAM2000TM.” This is more lenient by stating that “vaccination can 

be offered.” For that reason, it is a Category B recommendation. 

Dr. Weber (SHEA) emphasized that his only argument was that the recommendation did not 

provide enough precision to a hospital epidemiologist to know to whom they should offer 

vaccine, under what circumstances it should be offered, and who is responsible for making 

those decisions (hospital or local, county, state health departments). 

Dr. Decker (Sanofi Pasteur) indicated that since the time of original licensure of ACAM2000TM, 

a family of post-marketing safety studies has been underway. Some of these studies are 

completed, and others continue. The data that can be provided from those studies at this point, 

prior to the final analyses, was provided to CDC last year and were not materially changed. In 

total, nearly a million DoD personnel have been vaccinated and have been under surveillance 

in one or more of these studies. The information available is robust. The safety dataset is not 

likely to increase further in coming years due to the cessation of deployments to the Middle East 

and other factors, which means that DoD vaccinations will not occur at the same rate as in the 

past. DoD vaccinations represent 99.9% of all vaccinations in the US. 

Dr. Romero asked what DoD’s policy is regarding their physicians and nurses who administer 

this vaccine or care for individuals who receive the vaccination. 

Dr. Sergienko (DoD) replied that providers are vaccinated as well. 

Dr. Romero indicated that he was old enough to have received the vaccine as a child, and to 

have been a vaccinator during the last round of vaccinations. All vaccinators were vaccinated 

before they began to give the vaccine. Therefore, he wondered why this would be a Category 

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B rather than A recommendation and thought the recommendation about how to use the 

vaccine should be stronger. 

Dr. Petersen replied that the Category B recommendation specifically for vaccinators was 

simply because it has not been studied robustly. Though CDC is not aware of any infections 

that have resulted from exposures during vaccination in vaccinators, without a strong base of 

data to support that, the WG felt that it should be a Category B recommendation. However, he 

was not opposed to making it a Category A recommendation. 

Dr. Damon indicated that in the 2002 vaccination program, the decision to vaccinate the 

vaccinators was made because it was assumed that the vaccinators would also be part of the 

response. In the case of proposed recommendation, the individuals are simply taking care of 

patients who are in studies or who are being vaccinated. 

Dr. Petersen added that the volume of vaccine being administered by this specific vaccinating 

population is likely to be much lower, given that relatively few laboratory workers are receiving 

smallpox vaccine. Their cumulative risk of exposure while vaccinating may be lower than in 

other larger smallpox vaccination programs. 

Dr. Bennet requested additional information about the relationship between known cardiac risk 

factors and myo/pericarditis. Her understanding of myocarditis is that it could happen to 

anyone. 

Dr. Petersen replied that this was one of the more difficult issues the WG dealt with. It is 

accurate that there are not any known risk factors for attempting to predict who may have an AE 

of myo/pericarditis. That rationale used to support this recommendation is that if someone has 

this AE, they would likely have a more severe outcome based on known disease or known 

cardiac risk factors. 

Regarding Dr. Campos-Outcalt’s question, Dr. Plotkin (Vaccine Consultant) indicated that the 

mechanistic correlate of protection for smallpox vaccine is antibody. Antibody can last as long 

as 70 years and remains protective, or at least partially protective, during that time. The level of 

antibody that is protective has been estimated to be 1:32. The GMT of the ACAM2000TM is well 

above that. However, it might be more useful to give a percentage of those who have titers of 

1:32 or greater. There are no data on the cellular response, which is important in closing off the 

vaccinia replication. The ACAM2000TM vaccine apparently did that, which implies that they did 

develop a cellular response. ACAM2000TM may not have the same level of response, but as 

long as the level persists, it should be just as effective as Dryvax®. 

Dr. Kempe asked Dr. Petersen whether he could comment on the issue of whether the 

outcomes for vaccinia virus are substantially less severe and whether any of these analyses 

have been repeated based on those data. 

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Dr. Petersen responded that previous studies have assessed historical smallpox vaccine, and it 

has been observed that the take or cutaneous response to vaccination is ameliorated by 

previous vaccination. He did not believe this had been evaluated with ACAM2000TM, but it 

could be. That would be one example of direct demonstration of ACAM2000TM protecting 

against orthopoxvirus infection. 

Dr. Moore (AIM) asked how civilian laboratory personnel receive vaccines. They cannot call her 

office to get them. A graduate student contacted her from another state because they were 

beginning a project in which they were working with the vaccinia virus and could not obtain the 

vaccine, but she was unable to assist them. She also wondered whether any safeguards were 

in place to assure that laboratory personnel who have a Category A recommendation have 

access to the vaccine, and it is not simply a function of a facility that decides on their behalf 

whether they will be offered the vaccine. 

Dr. Petersen indicated that the policy note includes updated information regarding how to 

request the vaccine, for which CDC is the only source. The vaccine is made freely available, 

and explicit instructions regarding how to request smallpox vaccine from CDC’s Drug Services 

is included in the Policy Note. There should not be any barriers to receiving smallpox vaccine. 

He has heard that one of the primary barriers has been finding someone who is willing to 

administer the vaccine with the thought that the administrator needs to be vaccinated. Part of 

the thought in recommending that vaccinators for the laboratory worker population be offered 

vaccine rather than recommended to be vaccinated is to help ameliorate the potential for 

barriers to vaccinations for this population. 

Dr. Temte emphasized that at this point, there remained a number of unresolved questions 

pertaining to identification of who should receive the vaccine, whether having a laboratory in the 

community indicates that one of the local hospitals should have vaccinated staff on board, et 

cetera. He asked the members whether they wished to continue the session, or preferred for 

the WG to consider the issues further and engage in additional discussions during the October 

ACIP meeting. 

Dr. Harrison asked Dr. Petersen whether he felt he could address the issues raised and present 

a revised option the next morning. 

Dr. Petersen said he would be happy to discuss with Dr. Weber how to clarify some of the 

language and identify where there may be deficiencies. 

Dr. Temte proposed that they return to smallpox the next day, to which the members agreed. 

Revised Proposed Smallpox Vaccine Recommendations 

Brett W. Petersen, MD, MPH 

Medical Officer, Poxvirus and Rabies Branch, CDC 

Lieutenant Commander, U.S. Public Health Service 

During the second day of the June 2015 ACIP meeting, Dr. Petersen recapped the issues 

raised the previous day regarding the proposed smallpox recommendation and reviewed the 

proposed recommendation as revised. The following issues were raised and addressed: 

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 Change “worker” to “personnel” in policy note in an effort to be more inclusive. The WG 

agreed that this would be appropriate in order to be more inclusive and will make this 

change. 

 Revise the proposed recommendation for healthcare personnel. The WG agreed and 

proposed the following language: “Health-care personnel (e.g., physicians and nurses) that 

currently treat or anticipate treating patients with vaccinia virus infections whose contact 

with replication-competent vaccinia viruses is limited to contaminated materials (e.g., 

dressings) and persons administering ACAM2000TM smallpox vaccine who adhere to 

appropriate infection prevention measures can be offered vaccination with ACAM2000TM 

(recommendation category: B, evidence type 2).” 

 Regarding the responder population who may have already been vaccinated during the 

2002 smallpox vaccine program, the WG thought it would be reasonable to include the 

following statement in the revaccination section: “Public health and health care volunteers 

who were vaccinated as responders in the US Civilian Smallpox Preparedness and 

Response Program should refer to the October 2008 CDC Interim Guidance for 

Revaccination of Eligible Persons who Participated in the US Civilian Smallpox 

Preparedness and Response Program which can be found at 

http://emergency.cdc.gov/agent/smallpox/revaxmemo.asp. 

 Regarding post-exposure management, the WG did not feel that there were sufficient data 

to provide a strong recommendation for the possibility of post-exposure vaccination in 

persons who have been exposed to an orthopoxvirus. However, the proposed the following 

addition: “Persons with an orthopoxvirus exposure should be evaluated by a healthcare 

provider and clinical management decisions including post-exposure smallpox vaccination 

should be made on a case-by-case basis in consultation with public health authorities.” 

Vote: Smallpox Vaccine Use in Laboratory Personnel 

Dr. Riley made a motion to accept the wording, with the revisions as stated, for the use of 

smallpox vaccination in laboratory personnel. Dr. Romero seconded the motion. The motion 

carried with 15 affirmative votes, 0 negative votes, and 0 abstentions. The disposition of the 

vote was as follows: 

15 Favored: Bennett, Belongia, Bocchini, Campos-Outcalt, Harriman, Harrison, Karron, 

Kempe, Pellegrini, Romero, Reingold, Riley, Rubin, Temte, and Vazquez 

0 Opposed: N/A 

0 Abstained: N/A 

Day 1: Public Comment 

No public comments were offered during this session. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Agency Updates 

Centers for Disease Control and Prevention (CDC) 

Dr. Schuchat thanked Dr. Cindy Weinbaum for serving as the Interim Executive Secretary for 

the ACIP, and let the audience know that Dr. Ray Strikas will be joining ACIP as the Interim 

Executive Secretary following this meeting. The position for the permanent Executive Secretary 

will be posted soon. Regarding measles, the outbreak that originated in the Disney parks in 

California is officially over. However, imported cases do continue and public health is 

conducting considerable follow-up with each case individually. Early data show that there has 

been a substantial increase in adult measles, mumps, and rubella (MMR) vaccine uptake this 

year. It is gratifying that public awareness is increasing. More than half of the cases this year 

have been in adults who do not necessarily know or have their vaccine history. Since the 

February 2015 meeting, CDC initiated the Sierra Leone Trial to introduce a vaccine against 

Ebola together with the College of Medicine and Allied Health Sciences in Sierra Leone and 

other partners. Thus far, approximately 7000 healthcare and frontline workers have been 

enrolled and over 3300 have been vaccinated. That campaign is continuing in partnership with 

the Sierra Leoneans. 

Centers for Medicare and Medicaid Services (CMS) 

Dr. Hance reported that as a result of the measles outbreak, the Centers for Medicare and 

Medicaid Services (CMS) convened a call with all of its State Medicaid Directors in March 2015. 

CDC assisted with and participated in that call. The purpose of the call was to remind Medicaid 

Directors about the importance of maintaining a high level of vaccination coverage, and working 

with providers to ensure that all Medicare recipients also maintain vaccines. CMS is also 

working closely with CDC to try to improve Medicaid data to ensure that the Medicaid rate of 

coverage is clear. 

Department of Defense (DoD) 

Dr. Sergienko reported that the Department of Defense (DoD) continues to work on its new 

electronic health record (EHR). Based on recent conversations, he hopes that DoD’s 

Immunization Information System (IIS) will be better integrated with the state’s IIS and their 

programs. DoD is involved in post-marketing surveillance of the adenovirus vaccine. The study 

is complete and the results should be available shortly. Thus, far the data suggest a sharp 

decline in deaths. In terms of influenza vaccine for 2015-2016, DoD is partnering with the 

Office of Personnel Management (OPM) to improve vaccine rate uptake among federal 

employees on military installations by offering more information through the health benefits 

program and by offering more vaccines on installations. DoD is conducting a Japanese 

Encephalitis (JE) vaccine awareness campaign to increase vaccine uptake in Western Pacific 

areas that are at increased risk. Along with CDC and other partners, DoD is involved in the 

Ebola Vaccine Trials. The US Army Medical Research Institute of Infectious Disease 

(USAMRIID) was involved in fielding two of those vaccines. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Department of Veteran’s Affairs (DVA) 

Dr. Temte read the Department of Veteran’s Affairs (DVA) update into the record. The 

Veterans Health Administration (VHA) continues to work on several information technology (IT) 

immunization projects to improve documentation of immunizations in EMRs. Current efforts are 

focused on updates that will provide VA clinicians with greater detail about a patient’s 

immunization history, including vaccine administration dose, route, anatomical location, lot 

number, manufacturer, and which vaccine statement was provided to the patient. VHA 

released a set of updated national clinical reminders through their clinical decision report tools 

regarding two pneumococcal vaccines about two months ago, and plans to release new clinical 

reminders about Tdap, Td, and zoster vaccine later this year. VHA completed its annual 

seasonal influenza campaign, with 1.8 million doses administered to veterans. In addition, 

approximately 10,000 to 20,000 doses of influenza vaccine were administered to veterans 

during the 2014-2015 influenza season through a partnership between VHA and Walgreens. 

Food and Drug Administration (FDA) 

Dr. Sun reported that since the February 2015 ACIP meeting, the Food and Drug Administration 

(FDA) approved a new vaccine, QUADRACEL®, which is an acellular pertussis, diphtheria, 

tetanus, inactivated poliomyelitis vaccine (IPV) made by Sanofi Pasteur. This vaccine is 

indicated for children 4 through 6 years of age, given as a fifth dose in their routine 

immunization series or as a fourth or fifth dose of an IPV routine immunization series. On June 

30, 2015, FDA will be implementing the new pregnancy lactation rule for prescriber information. 

That means that all of the previous pregnancy categories will no longer be used. This is a 

revision of the way that the labels will look for drugs and biologics, including vaccines. The idea 

behind this is to better describe the benefits and risks when contemplating prescribing drugs or 

vaccines for use during pregnancy or breastfeeding women. A new category is included 

regarding reproductive potential for males and females, which will discuss considerations for the 

effects of drugs or vaccines on reproductive potential. This rule will be phased in for previously 

licensed products over the next three to five years, but any new applications received on or 

after June 30, 2015 will have to comply with this labeling requirement. FDA is working closely 

with CDC on the Ebola study in Sierra Leone, and with NIH on the Ebola vaccine study in 

Liberia. A vaccine advisory committee was convened in February 2015 to seek advice on 

potential ways to license an Ebola vaccine. 

Health Resources and Services Administration (HRSA) 

Dr. Houston reported that the national Vaccine Injury Compensation Program (VICP) had a very 

busy year processing claims in fiscal year 2014. A record number of non-autism claims were 

filed. In the last fiscal year, a total of 633 claims were filed with the VICP. Thus far, 496 claims 

have been filed in the 2015 fiscal year. The record set last fiscal year is anticipated to be 

surpassed this fiscal year. To date, there have been 390 adjudications of which 313 were 

compensable and 77 were dismissed. Awards to petitioners have totaled approximately $169 

million to date, and attorneys’ fees have totaled approximately $14 million. More data about the 

program can be obtained on the VICP website: www.hrsa.gov/vaccinecompensation/data. The 

program has been developing regulations to make changes to the Vaccine Injury Table. First, a 

Notice of Proposed Rule Making to propose several changes to the table has been developed 

and is being reviewed by HHS. The Final Rule, adding intussusception as an injury for the 

rotavirus vaccine, was published on June 23, 2015. A Public Readiness and Emergency 

Preparedness Act (PREP Act) declaration covering certain Ebola vaccines was signed on 

December 3, 2014 and became effective December 27, 2014. A few therapeutics were also 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

added to that declaration. People who have received the covered countermeasures are eligible 

to file a claim with the Countermeasures Injury Compensation Program (CICP). The CICP and 

the VICP continue to work on outreach efforts to make the public and providers aware of these 

safety net programs. 

Indian Health Services (IHS) 

Ms. Groom reported that the Indian Health Service’s (IHS) EHR currently has reminders for all 

of the routine age-based recommendations. PCV13 was recently added for those 65 years of 

age and older. More clinical decision support is being explored for high-risk conditions. The 

IHS EHR system currently includes Hepatitis B for diabetics, and IHS is working on decision 

supports for people with chronic liver disease. In terms of performance measures, IHS has 

changed its influenza measure. They have been monitoring influenza coverage among adults 

65 years of age and older for many years, but felt that it was time to change the performance 

measures for the agency to align with Healthy People 2020 to monitor influenza vaccine 

coverage across the IHS population. A developmental measure also is being explored to 

assess Tdap and influenza among pregnant women that will help to inform the reminder, and 

work continues on the development of a composite adult immunization measure to assess 

coverage for all of the age-based adult recommendations. In terms of influenza, the IHS 

remains frustrated with its fairly stagnant coverage levels. The Chief Medical Officer has 

requested that a focus be placed on this initiative, so an aggressive influenza plan has been 

developed and the regions are being asked to develop plans to help IHS achieve the Healthy 

People 2020 goal. 

National Institutes of Health (NIH) 

Dr. Gorman began with some words from the National Institutes of Health (NIH) Director, Dr. 

Collins, about his Precision Medicine Initiative, “Far too many diseases do not have a proven 

method of prevention or effective treatments. We must gain better insights into the biology of 

these diseases to make a difference for the millions of Americans who suffer from them. 

Precision medicine is an emerging approach for disease treatment and prevention that takes 

into account individual variability in genes, environment, and lifestyles for each person. While 

significant advances in precision medicine have been made for select cancers, the practice is 

not currently in use for most diseases. Many efforts are underway to make precision medicine 

the norm rather than the exception. To accelerate this, President Obama has now unveiled a 

Precision Medicine Initiative (PMI)—a bold new enterprise to revolutionize medicine and 

generate the scientific evidence to move the concept of precision medicine into everyday 

clinical practice.” 

The National Institute of Allergy and Infectious Diseases (NIAID) and NIH are also involved in 

the Ebola vaccine trials in Liberia. A large clinical trial to assess the safety and efficacy of two 

experimental vaccines to prevent Ebola infections is still open to volunteers in Liberia. The trial 

is being led by a recently formed Liberia-US clinical research partnership, and is sponsored by 

the NIAID. The study is called the Partnership for Research on Ebola Vaccines in Liberia 

(PREVAIL). PREVAIL is a Phase 2/3 study that was originally designed to enroll approximately 

27,000 healthy men and women 18 years of age and older. At least three vaccine candidates 

are being tested currently: NIAID-GSK chimpanzee adenovirus 3 (ChAd3-EBO Z)-based 

vaccine, the NewLink-MERCK Vesicular Stomatitis Virus (VSVdeltaG-ZEBOV)-based vaccine; 

and the Janssen-Bavarian Nordic AdVac® Eblola MVA-BN®. There are six major therapeutic 

candidates for Ebola: ZMappTM, an antibody cocktail that bonds and inactivates the Ebola 

virus; TKM-Ebola, a small interfering ribonucleic acid (RNA); BCX4430, a nucleoside analog 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

RNA polymerase inhibitor; acyclovir, a small molecule viral polymerase inhibitor with apparent 

broad antiviral properties; and favipiravir, which is licensed in Japan for pandemic influenza for 

which post-exposure efficacy has been shown in mice toward Ebola. An adaptive clinical trial 

has been constructed for evaluation of the therapeutic candidates of Ebola disease. This 

design was constructed by the Government of Liberia, the University of Nebraska, and Emory 

University. This trial will compare enhanced standard of care to enhanced standard of care plus 

a therapeutic candidate. ZMappTM is the first candidate. Other agents will be tested based on 

the supportive data availability of the product. The very heartening decrease in the number of 

new cases of Ebola makes completion of all of these trials much more difficult. 

In addition, there is a supplement to Clinical Infectious Diseases titled, “Including Pregnant 

Women in Clinical Trials of Antimicrobials and Vaccines,” which includes six articles [Volume 

59, suppl 7, December 15, 2014]. Many of the authors are previous or current ACIP members 

and liaisons. On the NIAID website, there is a slide show that highlights the notable scientific 

advances made by NIAID laboratories and NIAID-funded researchers at domestic and 

international institutions during the fiscal year 2014. Some advances have contributed to much 

needed vaccines and treatment for Ebola, HIV, and influenza. Others have expanded 

knowledge of rare conditions, such as prion disease and immunodeficiency disorders. All are 

representative of how public investment in biomedical research can advance science and 

benefit human health. Finally, NIAID Division of Microbiology and Infectious Diseases (DMID) 

clinical trials for vaccine candidates that are ongoing include a Hepatitis C vaccine trial, several 

influenza H7N9 trials, and an ongoing ZOSTAVX® trial for transplant patients. In development 

is a West Nile vaccine trial for which the Phase 1 study has been awarded to the Duke VTU 

site, and Investigational New Drug (IND) enabling studies to allow Phase 1 testing of a universal 

influenza vaccine candidate. 

National Vaccine Advisory Committee (NVAC) 

Dr. Orenstein reported that the National Vaccine Advisory Committee (NVAC) met on June 9­

10, 2015 and finalized three reports that should be available on the National Vaccine Program 

Office (NVPO) website in the near future. One of the reports deals with vaccine confidence, 

which is defined as “the trust that parents or healthcare providers have in the immunizations 

recommended by the ACIP, the providers who administer vaccines, and processes that lead to 

vaccine licensure and the recommended vaccination schedule.” The recommendation 

categories include better measurement, assessment, and tracking of parental attitudes toward 

vaccines; development of effective communication and strategies to build vaccine confidence; 

issues of HCP strategies, including development of materials for them to deal with parental 

concerns; a focus on curriculum for continuing medical education and physicians in training on 

vaccination issues; and developing of a working group to assess compensation issues for 

vaccine counseling. Other strategies included tightening of exemption policies and monitoring 

and support. The second report deals with human papillomavirus (HPV) vaccination, in which 

the NVAC endorses the President’s “Cancer Panel Report,” which is a comprehensive set of 

recommendations to improve HPV vaccine uptake and includes information pertaining to 

building communication strategies, strengthening immunization systems in adolescent 

immunization registries, and a review pertaining to whether the HPV vaccine schedule can be 

simplified to enhance compliance. The third report addresses the role of vaccines in 

antimicrobial resistance. The NVAC made a strong case to consider vaccines in efforts to 

combat antimicrobial-resistance bacteria, including having a liaison on the NVAC from the 

President’s National Strategy to Combat Antibiotic-Resistant Bacteria. 

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National Vaccine Program Office (NVPO) 

Dr. Gellin added that what Dr. Orenstein left out was that there is now a standard clause in 

every set of NVAC recommendations that states that the NVPO will figure out how to do all of 

this. He reported that the National Adult Immunization Plan (NAIP) is now in final clearance, 

which includes a focus on health IT and the importance of registries to keep the information 

flowing. The National Adult and Influenza Immunization Summit (NAIIS) was convened in 

Atlanta on May 12-15, 2015. The NAIIS is organized by CDC, the Immunization Action 

Coalition (IAC), and NVPO. One of the themes was the implementation of NVAC standards for 

adult immunization practices. Another theme was a focus on implementation science to 

address the fact that people know what they are supposed to be doing, but do not know how to 

do it. NVPO’s Interagency Vaccine Safety Task Force that includes HHS, VA, and DoD has 

developed a Vaccine Safety Scientific Agenda, which is located on the NVPO website. NVPO 

will soon release “A Year in Review” for 2014, which is a magazine style highlight of the many 

things that occurred in terms of vaccines and immunization. CDC’s Office of Women’s Health 

(OWM), the Office of Adolescent Health (OAH), and the NVPO have created a WebMD® 

program scheduled to begin at the end of June with a consumer/parent focus. 

Discussion Points 

Dr. Fryhofer (AMA) reported that during the June 2015 AMA House of Delegates meeting, the 

AMA voted in new policy to tighten the limitations on vaccine opt-outs. The House voted to 

support legislation eliminating non-medical exemptions for federally funded educational 

programs for children, and to support state medical societies in eliminating non-medical 

exemptions for childcare and school attendance in state statutes. The AMA Council on Science 

and Public Health (CSAPH) and its Council on Judicial and Ethic Affairs (CEJA) developed a 

joint report that laid out the scenarios. It was amazing testimony that demonstrated how the 

physicians in attendance were adamant about the non-medical exemptions being all that should 

be opted out of. This was a very different scene from what would have occurred several years 

ago. This shows the effect of measles and how things have changed. There is a great 

opportunity for immunizers to move with this momentum, given that the public now better 

understands the meaning of herd immunity and what can occur when people are not 

immunized. 

Dr. Weber (SHEA) reported that the University of North Carolina Hospitals has had a policy for 

a number of years to accept only medical contraindications to vaccines. As a condition of 

employment, all recommended ACIP vaccines are required for HCP. Two complaints were filed 

with the Equal Employment Opportunity Commission (EEOC), one regarding Tdap and the 

other MMR. In both cases, the EEOC ruled that if medical contraindications are accepted, 

religious objections must be accepted as well. Despite the policy, which was approved by the 

Attorney General of the State of North Caroline, it was overruled by EEOC. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Japanese Encephalitis Vaccine 

Joseph A. Bocchini, Jr, MD

ACIP, Workgroup Chair 

Japanese Encephalitis (JE) and Yellow Fever (YF) Vaccines Work Group

Professor and Chairman, Department of Pediatrics 

Louisiana State University Health Sciences Center 

Dr. Bocchini thanked Dr. Temte for his leadership and everyone for the opportunity to serve on 

ACIP the past four years, which has been a wonderful experience for him. 

During this session, Dr. Bocchini provided an update from the Japanese Encephalitis (JE) and 

Yellow Fever (YF) Vaccines WG regarding JE vaccine use. The inactivated Vero cell culturederived JE vaccine (JE-VC; Ixiaro®) is the only JE vaccine available in the US. JE-VC is 

manufactured by Valneva, formerly Intercell, and is distributed in the US by Novartis. 

Inactivated mouse brain-derived vaccine (JE-MB; JE-VAX) is no longer available in the US. 

In 2009 the FDA licensed JE-VC for use in adults and ACIP approved recommendations for a 

primary series in adults. In 2010, the MMWR Recommendations and Reports from 1993 were 

updated. In 2011, ACIP approved recommendations for use of a booster dose in adults based 

on new information and published a Policy Note in the MMWR. In 2013, ACIP approved 

recommendations for use of a primary series in children and published an additional Policy Note 

in the MMWR. 

Once the WG completed the YF vaccine objectives, the WG was tasked with updating the 

recommendations and guidance for use of JE vaccine. The WG’s JE vaccine objectives are to: 

 Review newly available safety and immunogenicity data for JE-VC; 

 Review epidemiology and risk of JE in travelers; 

 Review ACIP recommendations for use of JE vaccine in consideration of updated safety, 

immunogenicity, and traveler data with potential changes in recommendations to be 

presented to ACIP; and 

 Update MMWR Recommendations and Reports published in 2010 to include all the 

additional information. 

The updated MMWR Recommendations and Reports will include the removal of JE-MB vaccine 

information and recommendations, the addition of booster dose recommendations for adults, 

and the addition of the primary series recommendations for children. New JE-VC data to review 

and incorporate include the following: 

 Post-licensure safety data; 

 Use of a single primary dose in people who previously received JE-MB; 

 Increased and decreased intervals between the two primary series doses usually 

administered 28 days apart; 

 Co-administration with rabies and meningococcal vaccines; and 

 Duration of protection and additional booster dose recommendations. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Regarding additional expected data and events, by the end of 2015, the DoD post-licensure 

safety study data may become available. The manufacturer has requested a meeting with the 

FDA to discuss the acceptability of data for an alternate dosing schedule, co-administration, and 

booster dose indications. The manufacturer might submit proposed label changes in 2016 

related to these data. 

The ACIP JE and YF WG plans to present revised MMWR Recommendations and Reports to 

ACIP in October 2015 or February 2016. The timeline will depend upon the availability of data. 

Additional ACIP votes and policy notes may be needed in 2016 and 2017 as new indications 

are approved by the FDA. 

Pneumococcal Vaccines 

Introduction 

Nancy M. Bennett, MD, MS

Pneumococcal Vaccines Work Group Chair 

Advisory Committee on Immunization Practices 

Dr. Bennett began by thanking Dr. Temte for his great leadership. The Pneumococcal Vaccines 

WG has been very busy the last couple of years, and has really appreciated his support. 

She reminded everyone that the Pneumococcal Vaccines WG’s terms of reference are to: 

 Review current data on efficacy, effectiveness, immunogenicity, and cost-effectiveness of 

pneumococcal vaccines; 

 Review current recommendations considering up-to-date evidence, including 

epidemiological studies conducted post-licensure, and assess the strength of the evidence; 

and 

 Revise or update recommendations for pneumococcal vaccine use, as needed. 

Both 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal 

polysaccharide vaccine (PPSV23) are recommended for adults 65 years or older (ACIP 

Recommendation, August 2014), and individuals 2 through 64 years of age (ACIP 

Recommendation, Feb 2010, June 2012, June 2013) who have immunocompromising 

conditions, functional or anatomic asplenia, or CSF leaks or cochlear implants. The 

recommended sequence is PCV13 followed by PPSV23. PCV13 is recommended even if an 

individual previously received PPSV23. The recommended intervals vary by age and risk 

group, and the vaccine sequence: 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The focus of this session was harmonization of the recommended intervals between PCV13 

and PPSV23 across age and risk groups. The rational and evidence for the proposed changes 

to the recommended intervals between PCV13 and PPSV23, and the proposed changes to the 

recommendations for intervals between PCV13 and PPSV23 were presented for a vote. 

Intervals Between PCV13 and PPSV23 Vaccines:
 

Evidence Supporting Currently Recommended Intervals and Proposed Changes
 

Miwako Kobayashi, MD, MPH
 

Epidemic Intelligence Service (EIS) Officer

Respiratory Diseases Branch (RDB)

National Center for Immunization and Respiratory Diseases (NCIRD)
 

Centers for Disease Control and Prevention (CDC)
 

Dr. Kobayashi reminded everyone that currently in the US, two types of pneumococcal vaccines 

are being used: PCV13 and PPSV23. For individuals with underlying conditions 2 years of age 

and older and for all adults 65 years and older, administration of both vaccines in series is 

recommended to maximize protection against pneumococcal disease. When the two vaccines 

are recommended, PCV13 should be given first followed by PPSV23 whenever possible, as 

studies have demonstrated that the immune response was greater when PCV was given first. 

When PPSV23 is given first, there is a recommended interval before administering PCV13. 

However, under current ACIP recommendations, recommended intervals between PCV13 and 

PPSV23 are not consistent across age and risk groups, and also depend upon the sequence 

the two vaccines are given in. As Dr. Bennett outlined and showed in a table, the 

recommended intervals are different by age groups, risk groups, and the sequence in which the 

vaccines are given. 

Given the complexity of the recommendations, challenges associated with implementing the 

recommendations, and following many suggestions received by the Pneumococcal WG to 

harmonize recommendations across different age and risk groups, the WG considered the 

following question, “Would existing data allow harmonization of intervals between PCV13 

followed by PPSV23 and PPSV23 followed by PCV13 across age and risk groups?” In this 

presentation, Dr. Kobayashi reviewed the sequence of PCV13 followed by PPSV23, which is 

the preferred and recommended sequence in which the 2 vaccines should be given, and the 

sequence of PPSV23 followed by PCV13. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Regarding the intervals for the sequence of PCV13 followed by PPSV23, the following table 

summarizes the intervals that are currently recommended for different groups: 

There are potentially two ways to harmonize these recommendations, either by changing the 

interval recommended for children and adults with underlying medical conditions, or by 

changing the interval recommended for routine administration for adults 65 years and older. 

Since individuals with underlying conditions listed here are at higher risk of getting invasive 

pneumococcal disease (IPD), the WG did not think that the recommended interval for these age 

groups should be prolonged from the current 8 weeks. Therefore, the WG considered changing 

the interval for adults 65 years and older to be consistent with the younger age groups. 

However, review of existing literature did not support that change. Thus, harmonizing the 

interval within the same age group was considered; that is, with the interval recommended for 

the sequence of PPSV23 followed by PCV13 for adults 65 years and older. 

The WG considered several factors when determining whether the change in interval is 

warranted. The first factor related to implementation and programmatic challenges. As noted 

earlier, the current interval recommendation for PCV13 followed by PPSV23 for adults 65 years 

older is different from that of PPSV23 followed by PCV13. Different intervals have caused 

confusion among healthcare providers administering the vaccine. It also creates challenges in 

programming vaccine reminders in computer-based programs, as well as use as a quality 

measure. In addition, Medicare currently covers a different, second pneumococcal vaccine one 

year after the first vaccine is administered. This suggests that Medicare beneficiaries who 

received PPSV23 within a year of receipt of PCV13 would not be covered. 

The WG then reviewed the existing literature to determine whether the evidence would support 

changing the interval for the sequence of PCV13 followed by PPSV23 to 1 year or longer in 

adults 65 years and older. To answer this question, it would be ideal to review clinical efficacy 

studies designed to directly compare different intervals for the sequence of PCV13 followed by 

PPSV23. However, only limited data from immunogenicity studies are available and only one 

study included a direct comparison of intervals. The rest of the studies compared the immune 

response after the sequence of PCV (either 7-valent or 13-valent) followed by PPSV23, to the 

response after a single dose of either PCV or PPSV23 using various intervals. The WG 

compared these results from different studies to assess whether there is an association 

between the interval in PCV-PPSV23 series and immune response. The following table 

summarizes results from studies that provided data on comparison between the immune 

response after the PCV-PPSV23 sequence to the immune response after a single PCV dose: 

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In this comparison, of interest is whether the immune response after sequential administration 

would result in responses that are as good as or greater than the response after a single dose 

of PCV. Of note, the two studies referenced for the 1-year and 3- to 4-year intervals were 

designed to assess non-inferiority of immune response following the sequence compared to a 

single dose; whereas, the rest of the studies referenced in this presentation assessed whether 

the differences between the groups compared were statistically significant. While it is difficult to 

compare the results across different studies, immune response following the sequence appears 

to improve with increased intervals between the two doses. 

The following table summarizes results from studies that provided data on comparison between 

the immune response after the sequence of PCV followed by PPSV23, to the immune response 

after a single PPSV23 dose to assess whether adding PCV before PPSV23 would result in an 

improved immune response with the interval used in each study: 

Here, a tendency also is observed for studies using longer intervals to result in improved 

immune response, although again, direct comparisons across different studies are difficult to 

make. One study with direct comparison between different intervals was conducted among 

Alaska Native (AN) adults ages 55 through 70 years. The results were also included in the 

previous table. Participants were randomly assigned to three groups, which either: 1) received 

PPSV23 only, 2) received the sequence of PCV7 followed by PPSV23, 2 months apart, or 3) 

received the same sequence 6 months apart. Immune response was measured by IgG 

concentrations and opsonophagocytic assay for 5 pneumococcal polysaccharides. The results 

showed that the immune responses measured 2 months after the receipt of PPSV23 did not 

differ among the 3 study groups for any of the 5 pneumococcal serotypes measured. Of note, 

more injection site swelling that was statistically significant was noted in the group with a 2­

month interval compared to the group with a 6 month interval [Miernyk et al. CID 2008]. 

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In summary, none of the reviewed studies were designed to identify the optimal length of the 

interval between PCV13 and PPSV23. In addition, comparisons across studies are difficult to 

make given the differences in design or target population. The intervals used in the studies 

reviewed ranged from 2 months to 3 to 4 years8

. Comparisons of a response following a PCVPPSV23 series versus a single dose across studies utilizing these intervals showed that longer 

intervals, such as a year or longer6-7, may result in improved immune response compared to 

shorter intervals such as 2 months1 or 6 months1-5 . Of note, the one study that conducted direct 

comparison between 2 months and 6 months showed that the shorter interval was associated 

with increased reactogenicity that was statistically significant (p=0.01) [1

Miernyk, CID 2008; 

2

Musher, JID 2008; 3Goldblatt, CID 2009; 4Lazarus, CID 2011; 5MacIntyre, PLOS ONE 2014; 

6

Greenberg, Vaccine 2014; 7de Roux, CID 2008; 8Jackson, Vaccine 2013]. 

The following figure summarizes the incidence rate of IPD by serotype and age group from the 

2013 Active Bacterial Core surveillance (ABCs) data. These data are observed in a setting of 

PPSV23 coverage of approximately 60% among adults 65 years or older but before routine use 

of PCV13 in this age group: 

The blue portion of the bar represents the proportion of invasive pneumococcal disease caused 

by serotypes contained only in PPSV23 and not in PCV13, and is approximately 40% across all 

age groups. The overall burden of disease, as well as incidence of IPD caused by PPSV23­

only serotypes, is higher in older age groups. However, the potential change in the 

recommended interval will mostly impact those who are younger; that is, those who are turning 

65 as they are the ones who are more likely to be naïve to PPSV23 and, therefore, are more 

likely to receive PCV13 before PPSV23 and be affected by the change in the recommended 

interval. 

In conclusion, the WG considered that changing the interval between PCV13 followed by 

PPSV23 from the current 6 to 12 months to at least 1 year for adults 65 years and older would 

be appropriate for several reasons. First, the change will allow for harmonization of the 

recommendation with the interval for the sequence of PPSV23 followed by PCV13 for the same 

age group. Second, this will be consistent with the current CMS policy. Third, immunogenicity 

studies suggest that an interval of a year or longer between PCV13 and PPSV23 is appropriate 

and may lead to a better immune response compared to the one achieved with shorter 

intervals. The change in the recommended interval may result in up to 6 months increase in the 

risk window for invasive pneumococcal disease caused by serotypes only contained in 

PPSV23. However, 1 year is still within the currently recommended interval, and this change is 

likely to affect mostly the younger age group, naïve to PPSV23 and whose overall risk of 

pneumococcal disease is lower within this age group of 65 years and older. Therefore, the WG 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

proposed to change the interval between PCV13 followed by PPSV23 from the current 6 to 12 

months to at least 1 year. 

Regarding the intervals for the sequence of PPSV23 followed by PCV13, the following table 

summarizes the currently recommended intervals for the sequence of PPSV23 followed by 

PCV13 by different age- and risk- groups: 

To harmonize the recommendations, either the recommended interval for children with 

underlying conditions can be changed from 8 weeks or longer to 1 year or longer, or the 

recommended interval for adults can be changed from 1 year or longer to 8 weeks or longer. 

However, the recommendation of a 1 year or longer interval for adults was made based on data 

from immunogenicity studies suggesting blunting of immune response to PCV13 with shorter 

intervals between PPSV23 and PCV. Therefore, the WG reviewed the literature to determine 

whether evidence would allow a change in the recommended interval in children with underlying 

conditions to harmonize it with the interval recommended for the adult groups. 

There were a number of considerations with regard to harmonizing the recommendations. First, 

the proportion of children who potentially will be affected by this recommendation is small. 

Groups of children for whom this recommendation may be applicable include: 1) children who 

were 2 years or older who were indicated to receive PPSV23 before PCV7 became available in 

2000 (e.g., the current cohort of 17 to 18 year olds); and 2) children with underlying conditions 

who, for whatever reasons, did not receive any PCV13 or received incomplete PCV13 series as 

infants, and have already received a dose of PPSV23. Second, there are programmatic issues 

and practical aspects. The change will make the recommended interval different from the 

current interval for PCV13 followed by PPSV23. Conversely, the proposed changes would 

allow for harmonization of recommended intervals for this sequence across all age groups, and 

would harmonize intervals for both sequences for those with underlying conditions. In addition, 

the change is likely to affect only a small number of children, as explained earlier. Therefore, 

the WG felt that these proposed changes would not likely pose substantial implementation 

challenges for the majority of providers. 

The WG reviewed the existing literature to determine whether the evidence would support the 

change of the interval for the sequence of PPSV23 followed by PCV13 from 8 weeks or longer 

to 1 year or longer in children ages 2 through 18 years with underlying conditions. As stated 

earlier, it would be ideal to review clinical efficacy data that are designed to compare different 

intervals for the sequence of our interest. Since those were not available, the WG reviewed 

data from existing immunogenicity studies. Immunogenicity studies from adults have suggested 

that there may be a blunting of immune response to PCV when given after PPSV23, especially 

when the interval between the sequence was a year or less. Based on these data presented to 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

the committee during previous meetings, for adults, a 1 year or longer interval was 

recommended for PCV receipt post-PPSV23. 

In terms of whether the evidence supports the change of the interval for PPSV23 followed by 

PCV13 to ≥1 year for children 2 through 18 years of age with underlying conditions, limited data 

from immunogenicity studies are available. There are data suggesting blunting of immune 

response to PCV when the interval is ≤1 year after PPSV23 in adults1-7 . An interval of >1 year 

is recommended for adults. The WG reviewed available studies in children comparing the 

response after the sequence of PPSV23 followed by PCV7 to the response after a single dose 

of PCV7, to assess whether PPSV23 receipt before PCV7 administration given the interval 

used would result in decreased immune response. No studies using PCV13 were available for 

this comparison. The WG also reviewed one single arm study among children with sickle cell 

disease who have received PPSV23 prior to study enrollment. No comparison group was 

available in this study, but the response post PCV13 was evaluated, and the immune response 

post PCV13 was assessed by time since PPSV23 receipt [1

Lazarus, CID 2011; 2Musher, JID 

2008; 3

de Roux, CID, 2008; 4Jackson, Vaccine, 2013; 5Greenberg,Vaccine 2014; 6CrumCianflone, JID 2010; 7

Miiro, JID 2005]. 

Among the reviewed studies, there was no clear evidence of blunting of immune response 

when PPSV23 was given before PCV7 in comparison to the response after a single dose of 

PCV7. However, none of the studies had intervals that were less than one year. Regarding the 

results from a single-arm study that assessed children with sickle cell disease with a history of 

previous PPSV23 at least 6 months before enrollment, the median time since the receipt of 

PPSV23 was 2.9 years, with a range of 6 months to 11.8 years. The results showed that 

children were able to mount an immune response after administration of PCV13, and there was 

no correlation between time since PPSV23 and response to PCV13 [Montalembert, Pediatr 

Blood Cancer 2015]. 

In summary, none of the reviewed studies were designed to evaluate the optimal interval 

between PPSV23 and PCV13 in children with underlying conditions. From the reviewed 

studies, there was no evidence of blunting of immune response when PPSV23 was given 

before PCV7 compared to the response after a single dose of PCV7; however, all of these 

studies had an interval of at least 1 year between the two vaccines. The intervals evaluated 

were 1 year1

, 18–39 months2, 5 years3. Results from a single-arm study showed that there was 

no correlation between time since last PPSV23 and response to PCV13, but again, the 

minimum interval was 6 months [1

Blum 2000 Vaccine; 2Spoulou, Vaccine 2005; 3Mikoluc, Eur J 

Clin Microbiol Infec Dis 2008; 4

Montalembert, Pediatr Blood Cancer 2015]. 

In conclusion, the WG considered that changing the interval for the sequence of PPSV23 

followed by PCV13 from at least 8 weeks to 1 year for children 2 to 18 years with underlying 

conditions would be appropriate for several reasons. First, this would allow harmonization of 

the recommended intervals across all age groups with underlying conditions. Second, the 

proportion of children affected by this change would be small and this would only apply to those 

who already received a dose of PPSV23 and are eligible to receive PCV13. Third, this interval 

would avoid potential blunting of immune response to PCV13. Although the blunting was not 

evident from the reviewed studies, none of the studies had an interval shorter than 6 months. 

This change, however, will make the recommended interval different from the recommended 

interval for the sequence of PCV13 followed by PPSV23 for the same group. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Discussion Points 

Given that there have been PCV13 recommendations for 10 months, Dr. Temte wondered 

whether there was information about how many people over the age of 65 have received 

PCV13 followed by PPSV23 6 months later. To his knowledge, this was not occurring in 

practice in order to avoid the financial burden this would place on seniors. Dr. Kobayashi 

replied that they did not have this information in hand. 

Amy Groom (IHS) indicated that IHS does not have coverage data yet, but has programmed a 

reminder to give the PPSV23 at 6 months, because they felt urgently that the burden of disease 

in the IHS population was high enough that they wanted to administer that dose as quickly as 

possible. She remains concerned that there seemed to be a CMS policy issue that may be 

driving a change to 12 months rather than 6 months. 

Dr. Harrison shared Ms. Groom’s concern, expressing his curiosity about why CMS would not 

permit payment in accordance with ACIP guidelines. He also noted that the term “may be 

better” was being used. He requested a review of the data showing that it is better, because 

the data did not seem overly overwhelming. He wondered if what led to the statement was the 

6 of 7 versus 4 of 9 when the immunogenicity studies were reviewed. He also requested 

information regarding the GMTs. 

Dr. Kobayashi replied that there are no clinical data comparing the intervals directly. The 

recommendations are based on the immunogenicity studies. These studies used certain 

intervals, and were compared using different intervals. For example (referring to the slide Dr. 

Harrison questioned), the data presented were derived from a summary of studies using the 

sequence of PCV followed by PPSV23 using different intervals, compared to the immune 

response after a single dose of PPSV23. The 2-month interval and the 6-month interval were 

done in the same study. The investigators compared the immune response following PPSV23 

at 2 months between the intervals in one group, and at 6 months between intervals in another. 

That study did not show any statistically significant difference between the two groups in the 

responses. The result of the study that used a 1-year interval between PCV followed by 

PPSV23 showed that 1 out of the 7 serotypes measured had a greater result compared 

following the sequential dose versus the response after a single PPSV23 dose and 6 out of 7 

had a greater response after the sequential administration compared to a single PPSV23 

administration. Dr. Kobayashi indicated that she had not included the slide showing GMTs. 

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Dr. Schuchat noted that the vast majority of pneumococcal vaccines in adults are given in the 

fall. The incidence of pneumococcal disease in seniors is not flat during the year, so the 

incidence or risk of disease in a 6-month period could be quite different depending when the 6th 

month is. Therefore, she did not think the urgency about missing 6 months of coverage was 

necessarily a major issue. GMTs are not necessarily correlated with protection, so there is a lot 

of grayness regarding how to interpret the GMTs. 

Dr. Moore (SME) added that provider confusion seems to be driving the CMS issue. The 

number one question CDC has received since this recommendation is, “What is going on with 

these intervals? Why is it one way for this group and another way for that group?” He received 

an email the previous day from a provider who is in charge of programming their electronic 

medical records and decision support for pneumococcal vaccines, who asked whether ACIP 

was going to take up this issue. The CMS issue is not driving this. It is all about making it 

easier for providers to adhere to the recommendations. 

Dr. Temte reinforced Dr. Schuchat’s comment and invited those interested to go on the 

influenza website to look at the pneumonia and influenza death index. The seasonality of 

pneumonia deaths in this country is remarkable, and is largely confined to about a 4-month 

period every winter. 

Dr. Schuchat emphasized that there is an enormous amount of public and private health 

promotion every fall to promote influenza and pneumococcal vaccines. It would be much easier 

to take advantage of that in terms of trying to implement recommendations for a first or followup vaccination. It is also a good time to protect people before the intense season of pneumonia 

and influenza. The 6-month interval is not as practical from that point of view as a 1-year 

interval. 

Dr. Lett (CSTE) indicated that as one of the people who provides clinical decision support for 

their registry, they are changing these intervals. For them, it is black and white in terms of 

marking doses valid or not valid. Their registry is programmed not to recommend another dose 

if the interval is too short based on consultation with CDC. She asked for clarity about 

repeating a dose in those for whom the interval is too short between doses. 

Dr. Campos-Outcalt asked how many serotypes were measured and why, and if the studies Dr. 

Kobayashi presented were measuring the 23 in PPSV, the 13 in PCV, or the 7 in PCV. 

Dr. Kobayashi responded that the MacIntyre study measured the serotypes that were common. 

The results shown included a mixture of those studies for PCV7 and PCV13, which was the 

reason the PCV type was not specified. The serotypes they measured are usually the common 

serotypes between PCV and PPSV23. Sometimes, they only chose a few serotypes that were 

common based on various reasons, so the denominator is basically all of the number of 

serotypes that they measured that were common between the two. 

Dr. Campos-Outcalt said he was having a hard time reconciling the decision not to change the 

interval for the high risk groups, and he wondered what the rational was behind not making the 

intervals shorter for the older adults or longer for the high risk adults. 

Dr. Kobayashi clarified that these data were only from studies that were conducted in older 

adults. The studies in higher risk populations were conducted using short intervals. Basically, 

there is no good evidence to support making the intervals longer. The problem is basically the 

lack of good data to support an optimal interval. 

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Dr. Bennett noted that another consideration is that the majority of the over 65 group is 

relatively healthy; whereas, the people for whom this vaccine is being recommended in the 

younger groups are at high risk. 

Speaking as a pediatrician, Dr. Baker (IDSA) indicated that there are data for the 8-week 

interval in children at high risk. Speaking for the IDSA, there was robust interest among those 

in public health. The Chair of IDSA’s Public Health Committee is Dr. Geoffrey Duchin. One of 

the WG members is also a member of the Public Health Committee. If there were sufficient 

data, she believes they would show that an 8-week interval is too soon. From a practical point 

of view, people in the age group go to the doctor once a year if they are healthy. They go when 

CMS is going to pay for it. One of her colleagues went in at 6 months, found out she was 

healthy, and chose to return later when she learned that she would have to pay out of pocket. 

The IDSA’s position is that this is not perfect, but they are very supportive of the proposed 

recommendation. She asked whether there would be more data forthcoming. 

Dr. Kobayashi said that unfortunately, she did not have the answer to whether there will be 

additional data in the future that would offer a better basis for the recommendation. 

Dr. Schuchat added that the program is planning to conduct a post-licensure vaccine 

effectiveness study in adults. As mentioned before, the antibody levels are very difficult to 

interpret. The reality is that a lot of vaccination is being administered in a variety of intervals 

and sequences. However, more data will be forthcoming in the next few years. 

Dr. Whitley-Williams (AMA) noted that while coverage rates are 60% overall, coverage rates in 

Black Americans and Hispanics are approximately 45% to 46%. Although it does not directly 

address the issue of the intervals, if people 65 or older do not obtain their first vaccine, it is 

unclear how much difference this recommendation will make to the burden of disease, 

particularly in high risk populations. Also, under-represented minority populations tend to have 

higher complications in terms of diabetes, cardiovascular disease, asthma, et cetera. They 

certainly would fall into the high risk groups as well. This is obviously not an easy problem to 

solve. She emphasized the importance of recognizing the disparity. 

Dr. Paradiso (Pfizer Vaccines) explained that regarding a dose of conjugate vaccine, adults 

over 65 make a nice response and then it wanes quite rapidly; however, it is efficacious for 3 to 

4 years after that and probably beyond. A polysaccharide dose afterward is not required for 

that efficacy. The dose will renew that response post-conjugate vaccine, but it is not required 

for efficacy. The only reason for the polysaccharide vaccine is for the other 10 serotypes, not 

for the efficacy of the original 13. The discussion regarding the interval that achieves a higher 

booster after an initial conjugate vaccine is not really that important, because that booster is not 

needed for efficacy against the 13 types. The interval should be about programmatic issues 

and about what works best for getting people vaccinated, rather than efficacy against the 13 

types. 

Dr. Schmader (AGS) indicated for the record that the AGS strongly supported the 1-year 

harmonization. There has been a lot of confusion amongst patients and providers of older 

adults, and this will reduce the confusion. 

Dr. Temte expressed great appreciation for the IDSA and AGS comments, because they 

conveyed the type of information needed in terms of practicality. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

To further Dr. Harrison’s point, Dr. Grabenstein (Merck Vaccines) indicated that the equivalents 

are at Day 30 and the differences dissipate. Merck has a study underway to assess several 

dosing intervals between PCV13 and PPS23, which are anticipated to be available in 2016. 

Regarding Dr. Schuchat’s point, pneumococcal vaccine delivery spikes in the fall, coinciding 

with influenza, but vaccine delivery occurs all 12 months. Vaccination of adults should be 

available when it is convenient to them, even if that is in February, March, April, May, June, and 

July. That is hindered by reimbursement constraints, and it is enabled by education. When the 

patient presents, the clinician should evaluate and vaccinate them regardless of the clock. He 

agreed that the ethnic disparities are substantial and unacceptable. 

Dr. Reingold emphasized that part of the problem pertains to reimbursement by CMS, and he 

wondered whether there was a way to change CMS policy. 

Ms. Hance (CMS) responded that at this point, CMS does not feel that there are enough data. 

The decision was made based on the information currently available. As they heard throughout 

the session, there are no data supporting the intervals. The original decision was made by 

CMS based on a number of factors. First, the two inconsistent intervals must be defined. 

Medicare does not track which pneumococcal vaccine is given first. Given the two intervals, the 

common point was 12 months. In addition, as Dr. Schuchat mentioned, there is a very robust 

combined pneumococcal and influenza vaccine campaign that occurs once a year. It seemed 

logical to maintain that 12-month period and to continue to include the pneumococcal emphasis 

during the influenza and pneumococcal campaign. If there are additional studies, CMS is 

certainly happy to review them and to follow up with CDC and the ACIP. At this point, without 

further information regarding the intervals, CMS feels they have made the best decision 

possible at this time. 

Dr. Schuchat publically thanked CMS for the extremely speedy regulation they created 

regarding the conjugate vaccine. She reminded everyone that any type of change would likely 

be slow. 

Dr. Vazquez noted that while the proposed changes would harmonize the pediatric ages with 

the adult ages, it would do the opposite in terms of children only. In some ways, she thought 

this made it harder and more confusing for pediatric providers. 

Dr. Kobayashi replied that the WG did discuss this to some extent, but were also thinking about 

the fact that the recommendation addresses children with underlying conditions. These children 

will likely be seeing specialists who may have populations that cross the 18-year old age group. 

That issue, harmonization, and immunogenicity were all considered in terms of developing the 

proposed recommendation. 

Dr. Schuchat reminded everyone that the conjugate vaccine for children has been used for 15 

years and there is extremely high coverage. The actual number of children who will have 

received a polysaccharide vaccine prior to conjugate vaccine may not even be in the double 

digits; whereas, the vast majority of the pediatric issue pertain to very high risk children who 

should receive polysaccharide after conjugate vaccine. This is less about practitioner confusion 

than the desire for a shorter interval because these children are at very high risk. Of people 65 

years of age and older, 70% have already received the polysaccharide vaccine. Each year, a 

lot of people are aging into the 65 year old cohort who will be starting with the conjugate 

vaccine. 

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Dr. Temte pointed out that in primary care, the vast majority of children to whom this applies 

have sickle cell anemia. Children with other high risk conditions are being seen by pediatric 

infectious disease clinics, et cetera. 

Dr. Byington (AAP) indicated that the AAP has similar concerns as Dr. Vazquez about the 

confusion for pediatric providers. AAP would like to see real numbers. The 17 through 18 year 

old cohort is very small and will age out. However, they still exist and they are at the highest 

risk, often coming from populations with disparities like sickle cell disease and HIV. AAP is 

willing to delay the administration of the more effective vaccine from 8 weeks to a year for 

children who also require 2 vaccinations by AAP guidance. That is, they need to receive 2 

vaccines after the PPSV23. The delay is the concern for AAP. 

Regarding complexity and using clinical decision support with the immunization registry, Dr. 

Belongia indicated that the Marshfield Clinic has clinical decision support built into its registry, 

so this is all programmed into the rules. From a programming standpoint, this could result in a 

substantial amount of work. Which vaccine was given first is important in terms of programming 

this vaccine for children. 

Dr. Moore (AIM) indicated that AIM programmatically appreciates the simplicity. She was 

recently asked by their nurses to assess their own protocols because there was so much 

confusion in health departments. For programming purposes, it will be helpful to highlight in the 

catch-up schedule what the true minimum intervals are so that there are not flags for repeat 

vaccines that were given according to acceptable minimum intervals. That is, doses should not 

be considered invalid that were administered by the previous guidance. 

Dr. Loehr (AAFP) thought that from a practical point of view when assessing a patient, 

practitioners would be looking horizontally rather than vertically in terms of who is at high risk, 

rather than when they received PPSV23. 

Melvin Kahn (MERCK) indicated that the comments alluded to from providers reflected the type 

of feedback they have been hearing from the marketplace. Given the difficulties in ensuring a 

second dose of vaccine, covering 40% of IPD is not a trivial issue. 

Dr. Baker (IDSA) said, speaking for the IDSA and with respect to the AAP, IDSA is very 

interested in the topic and is fully supportive of the proposed changes, realizing that there are 

the issues mentioned. 

Regarding horizontal harmonization versus vertical, Dr. Pilishvili clarified that for adults 19 years 

of age and older with immunocompromising conditions, the WG members agreed that the data 

warranted a 1-year interval because immunogenicity studies show that there may be some 

evidence of a blunting of the immune response when PCV is even close to PPSV. In terms of 

children and this change, there are no data with an 8-week interval. Therefore, they could not 

assess whether the same concern existed in terms of potential blunting in pediatric studies 

because none of the studies reviewed utilized the 8-week interval. The interval was a year or 

longer. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Proposed Recommendations 

Tamara Pilishvili, MPH 

Respiratory Diseases Branch 

National Center for Immunization & Respiratory Diseases 

For each group for which the WG proposed a change, Dr. Pilishvili highlighted the current 

recommendation language and presented the proposed change. 

The current recommendation for the intervals between PCV13 followed by PPSV23 among 

adults ≥65 years of age is as follows: 

The dose of PPSV23 should be given 6 to 12 months after a dose of PCV13. If PPSV23 

cannot be given during this time window, the dose of PPSV23 should be given during 

the next visit. The two vaccines should not be co-administered, and the minimum 

acceptable interval between PCV13 and PPSV23 is 8 weeks. 

For adults ≥65 years of age with no previous pneumococcal vaccine (PCV13 or PPSV23), the 

WG proposed the following guidance on intervals for sequential use of PCV13 followed by 

PPSV23: 

A dose of PPSV23 should be given at least 1year following a dose of PCV13. The two 

vaccines should not be co-administered. If a dose of PPSV23 is given earlier than the 

recommended interval, the dose need not be repeated. 

The current recommendations for the intervals between PPSV23 followed by PCV13 among 

children 2 through 18 years with underlying conditions is as follows: 

Infants and Young Children <6 Years 

 History of complete PCV7 vaccination 

 For children who have underlying medical conditions, a single supplemental 

PCV13 dose is recommended through 71 months. This includes children 

who have received PPSV23 previously. PCV13 should be administered at 

least 8 weeks after the most recent dose of PCV7 or PPSV23 [MMWR 

December 10, 2010]. 

Children 6 Through 18 Years 

 Children aged 6 through 18 years who have not received PCV13 and are at 

increased risk for IPD because of anatomic or functional asplenia, including SCD, 

HIV infection, CSF leaks, cochlear implants, or other immunocompromising 

conditions; and who previously received ≥1 doses of PPSV23 should be given a 

single PCV13 dose ≥8 weeks after the last PPSV23 dose, even if they have 

received PCV7 [MMWR June 28, 2013]. 

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For children 2 through 18 years of age with underlying conditions, the WG proposed the 

proposed the following guidance on intervals for sequential use of PPSV23 followed by PCV13: 

A dose of PCV13 should be given at least 1 year following a dose of PPSV23. The two 

vaccines should not be co-administered. If a dose of PCV13 is given earlier than the 

recommended interval, the dose need not be repeated. 

Discussion Points 

Dr. Hahn (CSTE) thought the second sentence seemed confusing. It was not clear to her why 

there was another sentence saying the vaccine should not be co-administered, because the 

first sentence states that it should be given a year later and should rule out that possibility. 

Dr. Pilishvili clarified that this sentence was already in the recommendation. It was in response 

to multiple questions received and multiple scenarios in which a provider states that two 

vaccines were given together. It was not obviously clear even based on previous pediatric 

recommendations. Because these scenarios have arisen, the WG thought there should be 

clarification that these vaccines should not be co-administered. 

In terms of the pediatric proposed longer interval if PCV13 is being given after PPSV23, Dr. 

Rubin thought that historically there was an 8-week interval. However, that was before there 

was an appreciation for blunting. Even though the data are limited, there is no blunting with a 

1-year or longer interval. He thinks that is considerable, because the typical patient would be a 

sickle cell patient who is 3 or 4 years of age who perhaps has received the 23-valent vaccine. 

The concern is about protecting them over the next 5 to 10 years versus the next 10 months, 

which would be the interval. That is a reasonable concept based on the data and older 

individuals. 

Dr. Fryhofer (ACP) thought that, as a practitioner, the statement about not co-administering is 

such an important issue for the immunogenicity, it should remain. 

Ms. Pellegrini said she was having trouble with this as a layperson, because to her the first and 

last sentence said, “You should wait at least a year to give this vaccine, but really, do it anytime 

you want because there’s no minimum and we say you don’t have to repeat the dose. So, it 

doesn’t matter if you wait a year or not, or any amount of time, as long as they aren’t actually 

co-administered.” 

Dr. Pilishvili said the chain of thought as the WG was developing this recommendation 

language was that the main sentence would state the preferred interval, while the following 

sentences clarified what should/should not happen. What should not happen is that the 

vaccines should not be given together. The last sentence is essentially to allow for flexibility, 

because the evidence is weak. Whatever the evidence, the preferred statement is in the main 

sentence. 

Dr. Schuchat said that as an internist, it was surprising to her to learn about the incredible 

adherence and programmatic aspects of pediatric vaccination. In response to the layperson 

question, because she was a layperson 10 years ago, she would say that there are a number of 

pediatric vaccines that do not work if given too young, or at too short of an interval. In the 

pediatric practice and the immunization registries, the programmatic people who work on that 

are very focused on valid doses and invalid doses and making sure that children are complete 

and up-to-date on valid doses. The second red sentence really speaks to whether a dose 

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counts and if another one needs to be given, as opposed to the science that 8 weeks is 

probably going to work. Many people have had the 8-week interval. Going forward, the WG 

would like to give the direction to program in a 1-year interval. People are focused on what 

constitutes a valid/invalid dose because they are going to keep vaccinating until a patient has 

all of the valid doses recommended. 

Dr. Kempe thought the issues regarding harmonization of the adult and pediatric 

recommendations were entirely separate, and she wondered if they should separate them 

because it harmonizes on the adult side, but not the pediatric side. She thought Dr. Rubin’s 

comments were compelling, and said she would like to hear more from the Pediatric Infectious 

Diseases Society (PIDS) and the Infectious Disease Society of America (IDSA) about how 

strong a case there is. 

Dr. Vazquez said she would also like to hear more about this if, indeed, it was based on 

blunting. As a practitioner, if she read the second red line in the statement and her patient 

received PCV13 two weeks after PPSV23, then that dose would count. If the second red 

statement remained, it should state “if the interval between those two was at least 8 weeks.” 

Dr. Pilishvili said that would be like stating an 8-week minimum interval, which is what the 

recommendation was before. But, the way the 8-week interval was interpreted before was that 

if it was 7 weeks and 1 day, the dose would be invalidated and given again. There is no way of 

giving guidance on how/when to do that. 

Dr. Vazquez said somebody who had two doses that were not co-administered but were given 

within 2, 3, 4 weeks of each other, according to this, that would count. 

Dr. Pilishvili agreed. On a case-by-case basis, this is the recommendation CDC has been 

giving. There is no guidance to give on how to repeat doses; therefore, the instruction is “do 

not repeat.” Regarding what Dr. Schuchat was saying, there was discussion with the General 

Recommendations WG and the Immunization Services Division. All of the language that is in 

the pediatric recommendations about the minimum intervals applies to the same product. In 

other words, it is the minimum interval between the PCV doses and validation of that, because 

there are data that this results in the optimal immune response. There is a different issue here 

with 2 different vaccine products. 

Dr. Vazquez asked whether they had to vote on both of the proposed changes, or if the 

recommendations could be split. 

Dr. Temte replied that as an ACIP member, Dr. Vazquez could make a motion to split them. He 

said that being primarily an adult provider currently, the practicality of the adult recommendation 

trumped all of the science. His goal is to get his patients vaccinated. If he can do that in a 

simple way that is paid for, everyone is happy. On the other hand, he was hearing a lot of 

discussion, especially from their pediatric colleagues, that more information would be nice. He 

thought it would be reasonable to spit the two recommendations, and perhaps move forward 

with the adult vote during this session and have the WG bring back the pediatric 

recommendation during the October 2015 ACIP meeting. 

Dr. Bennett pointed out that the only objection the WG would have about bringing back the 

pediatric recommendation in October is that there will not be any additional data to present at 

that time. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Gemmill (NACI) suggested that for clarity, perhaps the word “inadvertently” could be added 

to the second red line to be very clear that this is not what is recommended as a practice, but if 

it occurs, the dose does not have to be repeated. 

Dr. Sawyer (PIDS) reminded everyone that this sequence of vaccines for children would apply 

to a very small number of now mostly late adolescents; therefore, he did not think they should 

spend too much time on this. Coupled with the adult data which show blunting and the lack of 

data in children, there is no biologic reasons to think children might not also have blunting. He 

thought they should accept the recommendation as presented. 

Dr. Kimberlin (AAP) noted that there have been no reports in the literature to show that the 

current recommendation of > 8 weeks of separation has resulted in failures. While there are no 

data to suggest that the 8 weeks is correct, there are also no data to suggest that there is 

blunting. The adult data are also limited, and there is no clinical correlate that suggests that 

there is a problem currently. The proposed change pertained to very small numbers of children 

who will soon age out if the rest of the schedule is being applied correctly. This means that they 

would be voting on a change that would introduce disharmony for the pediatric recommendation 

in what appeared to be an effort to harmonize across the columns rather than down. He 

thought that would impact major numbers of people. Though there may not be additional data, 

it may be beneficial for the pediatricians to consider and discuss this further internally and return 

later with a unified voice rather than the current disunity. 

Dr. Bocchini agreed that the pneumococcal recommendation was becoming increasingly more 

complicated over time. However, he thought they had been working to educate pediatricians to 

provide the vaccines based on the recommendations that exist currently. This is a time-limited 

phenomenon because these patients are going to age out. The new Red Book that was just 

published has the current recommendations. He thought they could work through this without 

changing the recommendations and without trying to change what pediatricians do currently, 

and that no one would be harmed. 

Dr. Zucker (NYC Immunization Program) offered some programmatic and practical 

considerations. As someone who writes standing orders for pharmacists and nurses, she has 

had tremendous problems trying to explain the pneumococcal recommendations. The easiest 

and clearest message for her to give practitioners in New York City is to say, “For children, the 

interval between pneumococcal vaccines is 8 weeks and for adults it is 1 year.” It also is 

simpler for their registries. If ACIP kept the pediatric recommendation as is, she would not have 

to reprogram her registry. They have not yet programmed all of the adult pneumococcal 

recommendations because they have had so much difficulty doing the programming. Based on 

the conversation, she will take out any minimal interval, and will accept any dose given after the 

other dose as that is the simplest approach. The sentence regarding co-administration is 

confusing and requires, because CDC also says that “if you do co-administer, you don’t need to 

repeat the dose.” When is “given earlier?” Is it 1 day after the previous dose? In fact, if it is 5 

minutes after 1 dose, it is still accepted. 

Dr. Baker (IDSA) agreed that there was a problem with the second and third sentences. 

Dr. Middleman (SAHM) pointed out that some older teens have issues in terms of being eligible 

for VFC. If there is a 1-year interval, it may mean that some teens can receive the first dose, 

but will not be covered a year later by the VFC. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Temte asked the ACIP members whether they wished to vote on both the adult and 

pediatric recommendations together, or separate out the adult recommendation and have the 

WG communicate further with ACIP’s pediatric colleagues to seek unanimity and return with the 

pediatric recommendation in October. 

Dr. Schuchat said that listening to the conversation, it seemed like the preferred motion was 

about the adult recommendation only. She pointed out that the pediatric issue pertained to 

more to catch-up rather than a routine recommendation, and ACIP could decide not to vote on it 

and have the WG bring it back at a later time. However, that did not mean they were obligated 

to bring it back for a future vote if they chose not to do so. The driving feature for the WG was a 

new vaccine for adults, and that being incredibly confusing. 

Dr. Temte said they could leave it to the wisdom of the Pneumococcal WG. He said that one of 

his favorite movies is the “Princess Bride” and the advice there is “Never get involved in a land 

war in Asia.” His advice to Dr. Bennett was always schedule more time for any pneumococcal 

discussions, because this is always the case. 

Vote: Pneumococcal Vaccines 

Dr. Belongia made a motion to adopt the adult language and leave standing the pediatric 

language. Dr. Vazquez seconded the motion. The motion carried with 15 affirmative votes, 0 

negative votes, and 0 abstentions. The disposition of the vote was as follows: 

15 Favored: Bennett, Belongia, Bocchini, Campos-Outcalt, Harriman, Harrison, Karron, 

Kempe, Pellegrini, Romero, Reingold, Riley, Rubin, Temte, and Vazquez 

0 Opposed: N/A 

0 Abstained: N/A 

Combination Vaccines 

Formation of Combination Vaccines Work Group 

Arthur Reingold, MD

University of California, Berkeley 

Chair, ACIP Combination Vaccines Work Group 

Dr. Reingold offered his gratitude to Dr. Temte for his chairmanship over the last few years. He 

reminded everyone that the ACIP has a number of WGs, some of which are permanent due to 

need and others of which are temporary. The Combination Vaccine WG is a new WG. Its 

existence should be relatively brief and is likely to conclude following the October 2015 ACIP 

meeting. 

The benefit of combination vaccines is the ability to combine equivalent component vaccines 

into single products to prevent more than one disease or to protect against multiple strains of 

infectious agents causing the same disease, reduce the number of injections, reduce concern 

regarding number of injections, and improve coverage and timeliness. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

The ACIP Combination Vaccines WG was formed in February 2015 to review published and 

unpublished data related to the safety and immunogenicity of 2 new combination vaccines: 1)
 

Quadracel® DTaP-IPV vaccine for children 4 through 6 years of age; and 2) an investigational
 

hexavalent pediatric vaccine (DTaP5-IPV-Hib-HepB), which is a 3-dose series for children at 2,
 

4, and 6 months of age.
 

Quadracel® is a diphtheria and tetanus toxoids and acellular pertussis adsorbed and inactivated 

poliovirus vaccine. It is intended as a second DTaP-IPV vaccine that is licensed for use in 

children 4 through 6 years of age. It is indicated for use as fifth dose in a DTaP series and
 

fourth or fifth dose in an IPV series in children who have received 4 doses of Pentacel® or 

Daptacel®. The Biologics License Application (BLA) was submitted to FDA on March 24, 2014.
 

The BLA was accepted by FDA for review on May 22, 2014. The FDA approved licensure on 

March 24, 2015.
 

A multicenter, randomized, controlled, Phase 3 clinical trial has been conducted comparing 

DTaP-IPV (Quadracel®) to separately administered DTaP (Daptacel®) and IPV (IPOL®

) 

vaccines in children 4 through 6 years who were primed with 4 doses of Daptacel® or Pentacel®. 

The Combination Vaccine WG will review the Quadracel® data and will be presenting 

information to the ACIP during the October 2015 meeting.
 

The investigational pediatric hexavalent vaccine includes antigens for diphtheria, tetanus,
 

pertussis and polio and is a combined product of vaccines made by Sanofi Pasteur and Merck.
 

It is intended as a 3-dose series (2, 4, 6 months). The BLA was accepted by FDA for review in 

October 2014, and licensure is anticipated in Fall 2015. Over the course of the summer, Sanofi
 

Pasteur and Merck will present information to the WG by teleconference. The WG will review
 

the safety and immunogenicity data, and the plan is to present the hexavalent pediatric vaccine 

to ACIP for an ACIP and VFC vote during the October 2015 meeting. A draft MMWR Notice to 

Readers is anticipated to be published in November or December 2015.
 

Discussion Points 

Gina Mootrey corrected one statement. The WG already reviewed the safety and 

immunogenicity of Quadracel® during its May 2015 teleconference. No concerns arose with 

regard to Quadracel®. The hexavalent vaccine information will be presented to ACIP during the 

October 2015 meeting. 

Human Papillomavirus (HPV) Vaccines 

Introduction 

Joseph A. Bocchini, Jr, MD

Chair, ACIP HPV Vaccine Work Group 

Dr. Bocchini reminded everyone that the 9-valent HPV (9vHPV) vaccine was licensed by the 

FDA on December 10, 2014. This was considered by ACIP during the February 2015 meeting, 

which was shortened by the closure of CDC due to threat of inclement weather. During that 

time, ACIP did vote on the major issues related to the 9vHPV vaccine. The recommendations 

were published in an MMWR Policy Note published on March 27, 2015. The one issue that was 

not considered was additional vaccination for those who completed an HPV vaccination series. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Related to 9-valent HPV vaccine, the following presentations were made to ACIP over the past 

year: 

 Epidemiology and burden of disease due to HPV types (February 2014) 

 Clinical trial data (February 2014, June 2014, October 2014) 

 GRADE (October 2014) 

 Health economic analysis (October 2014, February 2015) 

 Discussion of policy options (October 2014, February 2015) 

 9vHPV vaccine recommendations and vote (February 2015) 

The HPV WG continued to meet subsequent to the February 2015 meeting and reviewed 

evidence for additional 9vHPV vaccination regarding type-specific disease, clinical trial data, 

and cost-effectiveness data; and discussed additional transition issues that have occurred since 

licensure of the vaccine; and have discussed considerations for guidance for providers. 

During this session, presentations were given on the following topics: 

 9vHPV vaccination for persons who have completed an HPV vaccination series 

 Impact and cost-effectiveness of additional vaccination 

 Proposed guidance 

9-Valent HPV Vaccination for Persons Who 

Have Completed an HPV Vaccination Series 

Lauri Markowitz, MD 

HPV Vaccine Working Group

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

Centers for Disease Control and Prevention 

Dr. Markowitz began by recognition of Dr. Bocchini’s tenure on ACIP and as Chair of the HPV 

WG. He is rotating off of ACIP and stepping down as Chair of the HPV WG. He has served as 

Chair of the HPV WG since 2011, and has been a member of the WG since its inception in 

2004. He has been an integral part of this WG. He was Chair of the WG for the vote to include 

males in the routine recommendation schedule for HPV and the vote for 9vHPV, so he has 

played a strategic leadership role. Even though Dr. Bocchini is stepping down as Chair, he will 

remain on the WG as a member. 

During this session, Dr. Markowitz provided some background information including an 

overview of HPV vaccines, a review of the recommendations made in February 2015, and a 

discussion of issues related to program transition to 9vHPV vaccine. She then reviewed 

evidence related to the question of additional 9vHPV vaccination, type-specific attribution in 

cancers, and data from the one clinical trial of 9vHPV vaccine administered after a quadrivalent 

(4vHPV) vaccine series. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

As a reminder, the three licensed US vaccines are listed in the following table: 

All three are virus-like particle (VLP) vaccines. The bivalent (2vHPV) vaccine targets the 

cancer-causing types 16/18. The quadrivalent vaccine targets types 16/18 and types 6/11 that 

cause genital warts. The 9vHPV vaccine targets the same 4 types as the quadrivalent, as well 

as 5 additional cancer-causing types. The adjuvant differs between the 2vHPV and the 4vHPV 

and 9vHPV. Of note, about 99% of HPV vaccine administered in the US through 2014 was 

quadrivalent HPV vaccine. 

As noted earlier, the 9vHPV vaccine was licensed in the US in December 2014. It was 

recommended by ACIP in February 2015, and an MMWR Policy Note was published at the end 

of March. Updated AAP vaccine recommendations now available in the 2015 Red Book are 

consistent with the February 2015 ACIP recommendations. 

While the 4vHPV vaccine is licensed for females and males aged 9 through 26 years, the 

9vHPV vaccine currently is licensed for males only through age 15. At the time of the first 

application to FDA, 9vHPV immunogenicity trials in males 16 through 26 years had not been 

completed. However, immunogenicity data for males 16 through 26 years were presented to 

ACIP in October 2014 and were later submitted to FDA. In February 2015, ACIP recommended 

use of 9vHPV in the currently recommended age groups and through 21 years for males. 

However, 9vHPV use in males 16 through 26 years is currently off-label. 

The February 2015 recommendations that are now in the Policy Note state that routine 

vaccination is recommended at age 11 or 12 years with a 3-dose series. Vaccination is 

recommended through age 26 for females and through age 21 for males not previously 

vaccinated. Vaccination is recommended for men who have sex with men (MSM) and 

immunocompromised men through age 26. Vaccination of females is recommended with 

2vHPV, 4vHPV, or 9vHPV. Vaccination of males is recommended with 4vHPV or 9vHPV. 

ACIP recommendations also state the following: 

If vaccination providers do not know or do not have available the HPV vaccine product 

previously administered, or are in settings transitioning to 9vHPV, for protection against 

HPV 16 and 18, any HPV vaccine product may be used to continue or complete the 

series for females; 4vHPV or 9vHPV may be used to continue or complete the series for 

males. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Regarding programmatic issues related to the transition from 4vHPV to 9vHPV, following 

licensure of 9vHPV and the ACIP recommendation, 9vHPV was included in the VFC contract in 

April 2015. The contract price is $134 per dose, which is about $13 more than the contract 

price for 4vHPV vaccine. In May, the first time ordering of 9vHPV was possible on the VFC 

contract, just over 50% of awardees had placed orders that included 9vHPV. According to 

information from the manufacturer, as of June 2015, over 85% of managed care plans have 

decided to cover 9vHPV vaccine. Also of note, Merck intends to maintain 4vHPV in the US 

market until 9vHPV is approved by FDA for use in males 16 through 26 years and 6 months 

have passed from FDA approval of the male 16 through 26 year indication. Because of this, 

4vHPV vaccine is expected to be on the market until mid-2016 pending FDA approval of the 

male 16 through 26 year indication. 

CDC has provided some suggestions to awardees to assist with implementation during the 

transition from 4vHPV to 9vHPV vaccine. Providers who have 4vHPV vaccine in stock but 

prefer to vaccinate their VFC patients with 9vHPV vaccine should be able to order 9vHPV 

vaccine. For those providers who choose to implement 9vHPVvaccine but still have 4vHPV 

vaccine stock, doses of 4vHPV vaccine can be used to complete the series for patients who 

started a series with 4vHPV vaccine, or can be used in males since the additional protection 

from 9vHPV will mostly benefit females. 

The question of additional 9vHPV vaccine for persons who completed an HPV vaccination 

series was not discussed in February 2015 due to the abbreviated meeting. The MMWR Policy 

Note does not include information on this topic. There is no indication for additional 9vHPV 

vaccination in the vaccine label, although data are included in the label from the one clinical trial 

that addresses this issue. Additional 9vHPV vaccination has been a common question from 

vaccination providers and parents before and after 9vHPV vaccine licensure. 

As presented to ACIP last year, there is variation in the percent of cancers attributable to any 

HPV by anatomic site, ranging from 63% to over 90%. The majority of cancers at all sites are 

attributable to HPV 16/18, ranging from 48% to 80%. The percent attributable to the 5 

additional types in the 9vHPV vaccine ranges from a low of 4% for oropharyngeal cancers in 

males to 18% of vaginal cancers, one of the less common HPV-associated cancers1

. Data 

pertaining to the estimated annual number of cancers attributable to HPV 16/18 and the 5 

additional 9vHPV types are generated from the Saraiya study and the annual number of cases 

obtained from cancer registries. The majority of cancers that are attributable to HPV are 

attributable to HPV 16 and 18 at all anatomic sites. The largest number of cases due to the 5 

additional types are cervical cancers2 [

1

Saraiya et al. JNCI 2015;107; 2Based on years 2006­

2010 http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6349a11.htm and data from Saraiya et 

al. JNCI 2015;107]. 

In the US, approximately 64% of HPV-associated cancers are thought to be attributable to HPV 

16 or 18. HPV 16 or 18 account for 66% of cervical cancers and for the other cancers ranging 

from 48% penile cancers and 80% anal cancers. Of the HPV-associated cancers, 10% are 

attributable to the five additional types in 9vHPV (HPV 31, 33, 45, 52, 58). Of cervical cancers, 

15% are attributed to these types with a range of 4% oropharyngeal to 18% vaginal. Due to the 

differences in the percent of cancers attributed to HPV types at the anatomic sites, there are 

differences by sex. The 5 additional types account for about 14% for HPV-associated cancers 

in females and only about 4% for males. For cervical pre-cancer lesions of cervical 

intraepithelial neoplasia (CIN)2 or worse, approximately 50% are caused by HPV 16 or 18 and 

25% by the five additional types [MMWR 2015;64:300-4; MMWR RR 2014;63:1-30; Hariri et al. 

CEBP 2015;393-9]. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

ACIP reviewed data from the 9vHPV clinical development program during multiple meetings in 

2014. The 9-valent clinical development program included the pivotal efficacy trial; 

immunogenicity/immunobridging trials; concomitant use trials; and 9vHPV among females who 

were previously vaccinated with quadrivalent HPV vaccine (Protocol 006). The objectives of the 

Protocol 006 trial were to evaluate the safety of 9vHPV in prior 4vHPV recipients and to 

evaluate the immunogenicity of 9vHPV with respect to HPV 31, 33, 45, 52, 58 in prior 4vHPV 

recipients. There were 924 females in the study, which was a double-blind RCT. Vaccine was 

administered on a 0, 2, 6 month schedule. Antibody was measured at enrollment post-dose 1 

and post-dose 3. Although this study was conducted and that data were submitted to FDA, the 

manufacturer did not seek an indication for 9vHV vaccine among those previously vaccinated. 

The following graphic shows the study design, with the prior 3 doses of 4vHPV. There were at 

least 12 months between the last dose of 4vHPV and the first dose of 9vHPV in the study 

protocol. The green area shows Protocol 006 with the doses administered on a 0, 2, 6 month 

schedule: 

The findings of Protocol 006 were presented to ACIP last year. Post-dose 1, seropositivity to 

types 31, 33, 45, 52, and 58 was 98%, 95%, 68%, 94%, and 99% respectively. Of course, all of 

these were revaccinated and there is no information on persistence of antibody after this one 

dose. Sera were not collected post-dose 2. Post-dose 3, over 98% of prior 4vHPV recipients 

were seropositive to all 5 types. In terms of the GMTs, for the types in the 4vHPV vaccine (6, 

11, 16, 18) there was an increase in antibody post-dose 1 and no further increase after the third 

9vHPV dose. Remember, these individuals had already received 3 doses of quadrivalent 

vaccine targeting these 4 types. The GMTs for the 5 additional types appear lower than those 

for the 4 original types. Also, there was an increase in antibody after the third dose compared 

to after the first dose of 9vHPV vaccine. Except for type 31, the fold difference ranged from 2.3 

to 6. Listed on the slide were the injection site and systemic AEs that were observed among 

recipients of 9vHPV vaccine and had a frequency of greater than 1%. There was one SAE 

assessed to be due to vaccine in each group, tonsillitis and migraine, and both of these 

resolved 

[http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM4264 

57.pdf]. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

In order to further assess the results, data from Protocol 006 were also used in a cross study 

comparison. The objectives of this analysis were to compare the safety of the 9vHPV vaccine 

in prior 4vHPV vaccine recipients with 9vHPV vaccine in 4vHPV vaccine naïve females, and 

compare immunogenicity in the two groups. GMTs were lower in those who previously received 

4vHPV vaccine, with a ratio between .3 and .6. [http://www.fda.gov/downloads/BiologicsBlood 

Vaccines/Vaccines/ ApprovedProducts/UCM429166.pd]. 

Regarding injection-site AEs days 1 to 5 following each dose in protocol 006 and those who 

received 9vHPV vaccine but were naïve to vaccine in other studies, there appears to be a 

higher percentage of erythema (42% versus 32%) and swelling (49% versus 38%) in those who 

had prior 4vHPV vaccination compared to naïve women. 

In summary, an updated HPV vaccine Policy Note was published in March 2015 following the 

ACIP voted in February 2015. The 9vHPV vaccine was included in the VFC contract on April 1, 

2015. The transition to 9vHPV in public and private sectors is ongoing. The manufacturer 

expects 4vHPV vaccine to be on the US market until mid-2016. One trial evaluated 9vHPV 

vaccine in prior 3-dose 4vHPV vaccine recipients. After 3 doses of 9vHPV vaccine, over 98% 

of prior 4vHPV vaccine recipients were seropositive to all additional 5 types and there was an 

acceptable safety profile. In a cross study comparison of 9vHPV vaccine in prior 4vHPV 

vaccine recipients, 3 doses of 9vHPV vaccine resulted in lower GMTs for the 5 additional types 

compared with 3 doses of 9vHPV in HPV vaccine naïve females. The clinical significance of 

this is unclear, as there is no immune correlate of protection. The safety profile was similar, 

with the exception of higher rates of injection site reactions. 

Cost-Effectiveness of 9vHPV Vaccination for Persons 

Who Have Completed an HPV Vaccination Series 

Harrell Chesson, PhD 

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention 

Centers for Disease Control and Prevention 

Dr. Chesson briefly reviewed the health economics presentation from the February ACIP 

meeting, at which time a summary of the three models of 9vHPV in US and the costeffectiveness of routine 9vHPV vaccination versus routine 4vHPV vaccination were presented. 

The three models for 9vHPV in the US include the following: 

 US HPV-ADVISE Model [Brisson et al] 

 Based on published 9vHPV Canadian model, calibrated to fit US data 

 Merck Model [Weiss, Pillsbury, Dasbach] 

 Based on published 4vHPV model, expanded to include the additional types in 

9vHPV 

 Simplified Model [Chesson et al] 

 Based on published 4vHPV model, expanded to include the additional types in 

9vHPV 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

These models were used to estimate the cost-effectiveness of routine 9vHPV vaccination. The 

specific question the models addressed was, “What is the cost-effectiveness of a routine 9vHPV 

vaccination program for both sexes compared to a routine 4vHPV vaccination program for both 

sexes?” 

The following table shows the cost-effectiveness estimates for routine 9vHPV vaccination in 

terms of the incremental cost per quality-adjusted life year (QALY) gained: 

Model Incremental Cost Per QALY Gained 

No 4vHPV cross-protection With 4vHPV cross-protection 

HPV-ADVISE < $0 (cost-saving) < $0 (cost-saving) 

Merck < $0 (cost-saving) Not reported 

Simplified < $0 (cost-saving) $8,600 

The results are shown for two scenarios, with and without cross-protection for the quadrivalent 

vaccine. In the scenario of cross-protection, the 4vHPV vaccine was assumed to provide partial 

protection against the additional five types in the 9vHPV. The first column of results is for the 

no cross-protection scenario, for which all models suggest that 9vHPV vaccination is costsaving compared to routine 4vHPV vaccination. In the scenario of 4vHPV cross-protection, 

4vHPV provided partial protection against the additional five types in 9vHPV and the cost per 

QALY gained is quite low at $0 in the HPV-ADVISE Model and under $10,000 in the Simplified 

Model. 

To summarize the results already presented, the 9vHPV vaccine for both sexes compared to 

4vHPV for both sexes is likely cost-saving. The cost per QALY gained is less than $0 in most 

scenarios examined, and this was true in all three models examined. The cost per QALY did 

not exceed $25,000 in the sensitivity analyses. Most of the incremental benefits of 9vHPV 

vaccine are due to vaccination of females. 

In terms of the impact and cost-effectiveness of additional 9vHPV vaccination among prior 3­

dose 4vHPV vaccinees, the same three models used to address routine vaccination were used 

to address the cost-effectiveness of additional 9vHPV vaccination. The specific question 

addressed was, “What is the cost-effectiveness of providing 3 doses of 9vHPV to females who 

were previously vaccinated with 3 doses of 4vHPV vaccine?” All three models assumed that 

females aged 13 through 18 who had been vaccinated with the 4vHPV vaccine would be 

eligible for additional 9vHPV vaccination. All three models also assumed that additional 9vHPV 

vaccination would be a temporary program that would take place in the context of an ongoing 

routine 9vHPV vaccination program for both sexes. 

The following table shows the estimated impact and cost per QALY gained by additional 9vHPV 

vaccination: 

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For example, for the HPV-ADVISE model, it was estimated that about 1 million females would 

receive additional vaccination at an incremental cost of $432 million with a gain in QALYs of 

3,700. This works out to an incremental cost per QALY gained of about $117,000. The results 

for the other models are quite consistent with the results of the HPV-ADVISE model. 

In terms of why routine 9vHPV vaccination is so much more cost-effective than additional 

9vHPV vaccination, the incremental benefits are the same for routine and additional 

vaccination. That is, routine and additional 9vHPV vaccination both provide protection against 

the additional five types. The difference is in the incremental costs per person vaccinated. 

When switching from a routine 4vHPV program to a routine 9vHPV program, the incremental 

cost is simply the difference in the cost of the two vaccines or about $13 per dose. In contrast, 

the entire cost of the vaccine of $134 per dose is incurred to provide additional vaccination. 

Therefore, the difference in the incremental cost explains the difference in the costeffectiveness of these two vaccination strategies. 

Dr. Chesson presented results for sensitivity analyses from the HPV-ADVISE model, given that 

this model has performed the most extensive sensitivity analyses to date. The model accounts 

for uncertainty in the natural history by applying 50 different parameter sets. Each parameter 

set is run 40+ times. The results can differ from one model run to another due to chance, and 

80% uncertainty intervals calculated from 10th and 90th percentiles of these simulations. 

Because chance effects are relatively large compared to the effects of the additional 9vHPV 

vaccine program effects, these uncertainty intervals should be interpreted with caution. 

Regarding the cost-effectiveness of additional 9vHPV vaccination from the HPV-ADVISE model 

in terms of the cost per QALY gained, regardless of whether cross-protection is assumed for the 

4vHPV vaccine, the cost per QALY gained for 9vHPV vaccination ranges from about $7,000 to 

infinity. These extremes are not believed to be particularly realistic. What is occurring is that 

chance fluctuations in the model simulations are making the additional vaccination appear to be 

a lot worse or a lot better than it actually is. The actual interval of realistic estimates is believed 

to be much narrower than this, but a determination has not yet been made about how to do this. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

In summary, the cost per QALY gained by three doses of 9vHPV for prior 3-dose 4vHPV 

recipients is consistent across the three models at $117,400 in the HPV-ADVISE Model; 

$146,200 in the Simplified Model; and $156,100 in the Merck Model. As a reminder, these 

estimates are for the additional 9vHPV vaccination of females aged 13 through 18 years. The 

cost per QALY gained by additional 9vHPV vaccination would be higher for females over 18 

years of age and males of any age. 

In conclusion, routine 9vHPV vaccination for both sexes is likely to be cost-saving versus 

routine 4vHPV vaccination for both sexes. All three models also agree that additional 9vHPV 

vaccination would cost more than $100,000 per QALY gained. The cost-effectiveness could be 

even less favorable than estimated if, for example, it is possible to achieve higher routine 

9vHPV vaccination coverage than assumed in the models or if the people who receive 

additional vaccinations are the same ones who receive cervical cancer screening. 

Discussion Points 

Dr. Schuchat announced that the Supreme Court issued a ruling 6 to 3 in favor of upholding the 

Affordable Care Act (ACA). 

Dr. Karron noted that all of the economic models are based upon the necessity of three doses 

of the 9vHPV vaccine; however, she wondered what was known about one or two doses. 

Dr. Markowitz replied that as discussed during two previous ACIP meetings, there is an ongoing 

trial of two doses of 9vHPV vaccine. That trial is fully enrolled and the data will be analyzed 

over the next four to six months, so those data will be forthcoming. The study will assess two 

doses administered at 0, 6 months and two doses administered at 0, 12 months in 9 through 14 

year olds. That is being compared to a three-dose schedule in the age group that was in the 

efficacy trial. In protocol 006 (the trial of 3 doses of 9vHPV in persons who previously received 

4vHPV), antibody was determined after dose 1 and dose 3, but not after dose 2. Also, there 

was no follow-up of individuals who received a single dose because they all received doses 2 

and 3. 

Dr. Reingold asked whether it was possible to estimate how many cancers at different sites 

would be prevented by administering an additional three doses of 9vHPV vaccine to a cohort of 

women who have received 4vHPV vaccine. 

Dr. Chesson responded that this can be done and provided to ACIP. 

Dr. Markowitz added that this is somewhat different and not as straightforward as it is for other 

vaccines, because the cancers occur far out. During that time, 9vHPV vaccine will be used in a 

routine program and there will be some herd protection from that. 

Dr. Gemmill (NACI) reminded everyone that Canada uses a two-dose in some provinces, and 

their current dilemma regards what to do with the 9vHPV vaccine. 

Given the current level of uptake of 4vHPV vaccine and 9vHPV vaccine in vaccine-naïve 

individuals, Dr. Temte wondered what the effect would be of spending $400 million per year to 

enhance vaccination of vaccine-naïve people. That is, would increasing the first dose in girls 

from 50% to 75% and achieving a higher rate of completion have much more effect than 

administering additional doses in terms of a stable amount of public expenditure? There 

remains a struggle to administer even one dose to half of the US population of either vaccine. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

His fear is that programs to revaccinate people are going to target a group that is already 

getting the vaccine, and may not be the group that really needs to be vaccinated in the first 

place. 

Dr. Chesson replied that the cost-effectiveness of additional 9vHPV vaccination compared to an 

intervention to increase coverage of routine 9vHPV vaccination could be modeled. He said his 

bet would be that the intervention to increase routine 9vHPV coverage could incur substantial 

program costs and still come out ahead of additional 9vHPV vaccination in terms of costeffectiveness and impact. 

Proposed Guidance 

Lauri Markowitz, MD 

HPV Vaccine Working Group 

National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention

Centers for Disease Control and Prevention 

To summarize this session, evidence is from one RCT that evaluated the immunogenicity of 3 

doses of 9vHPV vaccine versus placebo among prior 3-dose 4vHPV vaccinees. After the third 

dose, seropositivity for all 5 additional types was over 98%. There has been no formal noninferiority immunobridging evaluation. However, in a cross study comparison, the GMTs for the 

5 additional types after 3 doses were lower than those after 3 doses of 9vHPV vaccine in HPV 

vaccine naïve women. The clinical significance of the lower titers is not known, because there 

is no immune correlate of protection. No safety concerns are apparent. In the cross study 

comparison, there were higher rates of injection site reactions compared with 9vHPV vaccine in 

HPV vaccine naïve females. 

The benefit of protection against the 5 additional types would be mainly for females for the 

prevention of cervical cancers and precancers. The cost per QALY gained is over $100,000 for 

the additional 3 doses among females 13 through 18 years of age. There is a higher cost per 

QALY for females over age 18 years, and for males at any age. In contrast, the models have 

shown that routine 9vHPV vaccination for females and males in the US is cost-saving compared 

to a quadrivalent HPV vaccination program. 

The WG felt that the highest priority was raising 9vHPV vaccine coverage for the primary 

vaccination series. A variety of programmatic issues were considered for routine and additional 

vaccination. As was mentioned and most ACIP members know, 2013 coverage for 13 through 

17 year olds for one dose was approximately 57% and for three doses 38%. So, a lot of work 

has to be done to raise coverage in the US. The economic analyses and considerations 

reviewed varied. Some WG members placed more weight on the health economic analyses 

than others. The WG also noted that cervical cancer screening continues to be recommended 

for women aged 21 through 65 for vaccinated and unvaccinated women. 

The WG members were not in favor of a recommendation for routine additional 9vHPV 

vaccination of persons who previously completed a 3-dose HPV vaccination series. However, it 

was felt that guidance and information are needed in a variety of areas. First, although some 

recommendations are provided in the Policy Note for persons who started the series with 

another vaccine, further guidance has been requested by vaccination providers since 

recommendations were published. Second, for persons who completed a 3-dose HPV 

vaccination series, WG members felt that clarification is needed regarding what data are and 

are not available. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

As mentioned earlier, questions about additional vaccination have been common, both before 

and after licensure. Some parents and providers are interested in additional protection against 

the 5 additional types. Some parents and providers may be just seeking information and 

guidance. The WG felt this was partly because of provider recall regarding the pneumococcal 

conjugate vaccine (PCV) 7 to 13 transition, but there are differences between that transition and 

the HPV vaccine transition as reflected in the following comparison: 

There are no plans for an additional HPV vaccine Policy Note in the MMWR with this guidance. 

Instead, information will be posted on the CDC website. There will be a link from the ACIP 

website recommendation page to this information, as well as a notice in the MMWR with a link 

to this information. Examples of guidance for providers has been drafted for three areas: 1) 

9vHPV vaccination for persons who started the series with another HPV vaccine product; 2) 

9vHPV vaccination for persons who completed an HPV vaccination series; and 3) 9vHPV 

vaccination and information available. 

Example 1: Vaccination for Persons Who Started the Series with Another Vaccine 

Product 

If a series was started with quadrivalent HPV vaccine or bivalent HPV vaccine, can it be 

completed with 9-valent HPV vaccine? 

Yes, ACIP recommendations state that 9-valent HPV vaccine may be used to continue 

or complete a series started with a different HPV vaccine product. 

Are additional 9-valent HPV vaccine doses recommended after a series started with 

quadrivalent or bivalent HPV vaccine and completed with 9-valent HPV vaccine? 

There is no ACIP recommendation for additional 9-valent HPV vaccine doses for 

persons who started the series with quadrivalent or bivalent HPV vaccine and completed 

the 3-dose series with 9-valent HPV vaccine. 

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If a series was started with quadrivalent HPV vaccine or bivalent HPV vaccine and will be 

completed with 9-valent HPV vaccine, what are the intervals for the remaining doses in 

the 3-dose series? 

 The current recommended HPV vaccination schedule is for the second dose to be given 

2 months after the first dose and the third dose 4 months after the second dose (6 

months after the first dose). ACIP does not state maximum intervals between HPV 

doses. 

 Antibody titers have not been found to be diminished after longer than standard intervals 

between doses. Data from other HPV vaccine studies show equal or higher antibody 

titers when 2 doses were administered at an interval of 6 months compared with 2 

months. 

–	 An ongoing immunogenicity study is evaluating 2 doses of 9-valent HPV vaccine 

separated by an interval of 6 or 12 months. 

Example 2: Vaccination for Persons Who Completed an HPV Vaccination Series 

Is additional vaccination with 9-valent HPV vaccine recommended for persons who have

completed a 3-dose series of either quadrivalent or bivalent HPV vaccine? 

 There is no ACIP recommendation for routine additional 9-valent HPV vaccination of 

persons who previously completed a quadrivalent or bivalent vaccination series. 

If a person desires protection against the 5 additional types prevented by the 9-valent

HPV vaccine and has completed a 3-dose series of HPV vaccine, what issues should 

be considered? 

 The benefit of protection against the 5 additional types targeted by 9-valent HPV 

vaccination is mostly limited to females for prevention of cervical cancers and 

precancers. This is because only a small percentage of HPV associated cancers in 

males is due to the 5 additional types in 9-valent HPV vaccine. 

 Available data show no serious safety concerns in persons who were vaccinated with 9­

valent HPV vaccine after having received quadrivalent HPV vaccine. 

 Cervical cancer screening is recommended beginning at age 21 years and continuing 

through age 65 years for both vaccinated and unvaccinated women. 

Example 3: Information Available 

What data are available on efficacy and immunogenicity of 9-valent HPV vaccination for

the 5 additional types, when administered after a complete 3-dose series of another HPV 

vaccine product? 

 In the one immunogenicity trial, 3 doses of 9-valent HPV vaccine vaccination (on a 0,2,6 

month schedule) were given to females who had completed a 3-dose quadrivalent HPV 

vaccine series; the first dose of 9-valent HPV vaccine was administered at least 12 

months after completion of the quadrivalent vaccine series. 

–	 After 3 doses of 9-valent vaccine, over 98% of vaccinees developed antibody to 

all 5 additional types. Antibody was also measured after the first dose of 9­

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valent HPV vaccine; most but not all vaccinees developed antibody against all 5 

additional types. Antibody was not measured after the second dose. 

In a cross study comparison, geometric antibody titers for the 5 additional types 

after 3 doses of 9-valent HPV vaccine were lower, 25-63% of those in persons 

who received 3 doses of 9-valent HPV vaccine without prior HPV vaccination. 

The significance of the lower antibody titers is not known because there is no 

immune correlate of protection. 

What data are available on safety of 9-valent HPV vaccination when administered after a 

complete 3-dose series of another HPV vaccine product? 

 In a randomized trial, 9-valent HPV vaccine was compared with placebo in females aged 

12-26 years who had previously received 3 doses of quadrivalent HPV vaccine. Among 

the 608 who received 9-valent HPV vaccine, there was an acceptable safety profile. 

 Compared to persons in other studies who were vaccinated with 9-valent HPV vaccine 

without prior HPV vaccination, those who received 9-valent HPV vaccine after a 3-dose 

quadrivalent vaccine series had higher rates of injection site swelling and redness. 

 Otherwise, the safety profiles of 9-valent vaccine given to HPV vaccine naïve persons 

and of 9-valent vaccine given to persons who had previously completed a 3-dose series 

were generally similar. 

Discussion Points 

Dr. Middleman (SAHM) noted that SAHM’s major concern pertained to ensuring that there is no 

discrepancy for those who would like to be revaccinated in terms of those who can and cannot 

afford to do so. She assumed that it would be covered by the VFC since it is approved, but she 

was curious to know from insurance companies what their policies might be. 

Dr. Netoskie (AHIP) said his understanding was that a three-dose series would be covered 

regardless of the combination. If ACIP made no recommendation and it offered no significant 

additional advantage, he assumed the cost would be the responsibility of the patient. 

Dr. Orenstein (NVAC) said that was his concern as well. The way he read it, one would have to 

pay out-of-pocket for revaccination. Based on the data presented, it appeared that about 3000 

cancer cases might be preventable. Cancer has been one of the major concerns. In his 

opinion, there should be at least a Category B recommendation. 

Dr. Kimberlin (AAP) reported that families and pediatricians are already asking this question. 

He thought the AAP would need to provide some guidance. If there is no recommendation but 

there is information to show that the vaccine is safe and adds some degree of efficacy, those 

would can afford it will get it and those who cannot will not get it. Whereas, a Category B 

recommendation from ACIP would tie in those funds and would equalize the potential 

discrepancy. The AAP would be interested in working with the WG to develop such language if 

the ACIP is interested. 

Dr. Moore (AIM) added her voice to the suggestion that the WG and ACIP consider a Category 

B recommendation. Especially in light of the discussions and numbers from the previous day, 

these numbers seem rather favorable in terms of the volume of cancer cases that could be 

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prevented. Although not as sudden and dramatic as “out of the blue” deaths, these are 

agonizing deaths for families of young adults throughout the country. If there are those who 

wish to avail themselves of additional safe protection to prevent that risk even further, that 

opportunity should be made available to them. 

Dr. Fryhofer (AMA/ACP) thought the guidance statement would be very helpful for practitioners, 

and wondered when it would be posted on the website. 

Dr. Markowitz thought the guidance could be placed on the website in a matter of weeks, 

although it will take longer for the announcement in the MMWR. 

Dr. Harrison asked whether the WG discussed the plusses and minuses of a Category B 

recommendation, and if so, if she could summarize the discussion. 

Dr. Markowitz replied that they did, and a GRADE analysis was conducted as well. Some WG 

members favored a Category B recommendations and some did not. 

Dr. Ault (ACOG) noted that Dr. Chesson had a publication in the past couple of years that 

stated that about $6 billion is spent on HPV and related cancers, while approximately $5 billion 

is spent on screening for cervical. He wondered whether that was also in the model. 

Dr. Chesson responded that the models do take into account the vaccines’ effect on reducing 

the costs associated with screening, and assume that cervical cancer screening will continue 

into the future. 

With all due respect to trying to eliminate as much cancer as possible, Dr. Riley thought if all of 

the time, energy, funds, and time were focused on vaccinating more young girls and boys, the 

results might be much better. She feels very strongly that spending a lot of energy on the 

population that has already been fully vaccinated diverts attention. Many efforts have been 

made only to achieve a 50% vaccination rate among the eligible population. Putting the effort 

into vaccination of a much greater number of people will make a major difference. 

Dr. Belongia pointed out that applying more generally the equity issue and the fact that there is 

some benefit to receiving additional doses of 9vHPV, a logical conclusion could be reached that 

every vaccine licensed by the FDA should at least get a Category B recommendation because 

they are safe and effective. 

Dr. Middleman (SAHM) echoed that SAHM supports the recommendation of immunization with 

one kind or another. They want the focus on getting everyone immunized at least once. Their 

concern is the equity concern and ensuring that there is not a disparity when some patients truly 

want to be revaccinated. They are not suggesting that the focus move to revaccination. They 

are simply suggesting that it be an option available to those who desire it. 

Dr. Harrison said his point regarded whether it was a zero sum game. He fully recognized that 

uptake was poor. However, he wondered whether a Category B recommendation would divert 

attention away from the focus of putting the effort into vaccination of a much greater number of 

people with one vaccine. 

Dr. Baker (IDSA) said she understood lack of consensus in a WG, recognizing that this was 

sometimes because there were not enough data. She wondered whether Dr. Markowitz 

anticipated that the 2-dose data that would be available by October would help the discussion. 

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Dr. Markowitz said while she was hopeful the data would be available in October 2015 

regarding the 2-dose trial, she was not 100% sure that they will be available at that time. 

Enrollment is complete, but they have not been given a guarantee that they will see those data 

in October. It might be February 2016, at the latest. While those data will be helpful, they are 

not specifically relevant to the additional vaccination question because they are in vaccine 

naïve individuals. It is known that antibody titers are lower in people who have received 9vHPV 

vaccine after 4vHPV vaccine. Also important to note is that all of the data on 2 doses, including 

the one quadrivalent vaccine trial from Canada are just for 9 through 14 year olds. 

Regarding equity, Dr. Sawyer (PIDS) thought that VFC providers could administer as many 

vaccines as they wished as long as there is no recommendation. For example, could they give 

10 MMRs and have all of them covered by VFC? 

Dr. Moore (AIM) indicated that AIM runs the VFC program in Tennessee and they do not count 

the number of doses being given. Practitioners just tell them how many doses they need to 

order. This is not cross-checked with individual patients to determine whether the required 

number of doses are given to each patient. If this was done all of the time and someone 

reported a physician, they might have to have a conversation about it. 

Dr. Bennett said she was very sensitivity to the equity issue, and this reminded her of the 

Virginia Slims “You’ve Come a Long Way Baby” advertisements. That was about equity and 

smoking. It seemed to her that the WG had determined that giving additional doses is not 

valuable. She did not believe they should be worrying about equity for something they did not 

believe to be the right thing to do. 

It seemed to Dr. Temte that it might be best for the WG to consider this further, given the 

divided interest in a Category B recommendation. 

Dr. Schuchat pointed out that the FDA approval of the 9vHPV vaccination was not for the 

indication of revaccination. The transition plans are going to be somewhat prolonged compared 

to the transition with the PCV7/13 swap out. CDC views implementation guidance differently 

from ACIP policy. CDC envisions implementation guidance in terms of states ordering as the 

agency’s responsibility, so the idea is to post commonly asked questions and answers in this 

transitional period. This is not even an FDA-approved indication. This is simply a commonly 

asked questions from clinicians and programs. The goal is to disseminate information about the 

evidence, as well as practical answers to the questions being posed. 

Dr. Bocchini clarified the WG deliberations, pointing out that 9vHPV vaccine clearly has benefits 

and that was not in question. They key issues related to strong opinions in the WG regarding 

whether a focus on revaccination would impede the primary purpose to get people vaccinated 

in the first place. There are strong opinions on both sides. If the February 2015 meeting had 

not been truncated, the session would have included information of doing one or the other 

based on the GRADE analysis and showing ACIP that there were differences of opinion among 

WG members about this in order to ask ACIP to weigh in on a Category B recommendation. It 

is certainly reasonable for the WG to provide that additional information to help ACIP make that 

decision. 

Dr. Rubin pointed out that the two are not mutually exclusive. Guidance could be provided and 

subsequently, a decision on a Category B recommendation could be made. 

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Dr. Temte thought the intent was for the guidance to be provided. As a clinician, he said he 

found everything CDC develops to be very helpful. The question regarded whether the 

members felt that additional time and effort should be put into make a decision about a 

Category B recommendation, although ACIP tries desperately not to use Category B 

recommendations very often. 

In terms of process, Dr. Campos-Outcalt wondered what the result of doing nothing during this 

session would be. 

Dr. Temte pointed out that for zoster vaccine, there was no vote on anticipation of changing the 

age. For Tdap, there was no vote on consideration of revaccination. By not taking a vote, ACIP 

confirmed current policy for those decisions. By not taking a vote during this session, they 

would affirm the fact that ACIP recommends one of the three vaccines available, with no 

preference expressed for any one of the vaccines. They would also not go beyond the FDA 

licensure in terms of promoting revaccination. 

Dr. Campos-Outcalt asked whether those not in agreement with the current statement needed 

to make a motion to send it back to the WG, or make a motion to make it a Category B 

recommendation. Otherwise, it would stand as proposed. 

Dr. Markowitz clarified that there is no ACIP recommendation for routine additional vaccination. 

The guidance language also addresses what needs to be considered if someone does want 

additional protection. This was included to let people know the safety data available and that 

for males, there is little additional protection. 

Dr. Harrison favored further discussion about the possibility of a Category B recommendation, 

reiterating the concern about whether a Category B recommendation may have a negative 

effect on the efforts to get naïve people vaccinated with the first series. 

Dr. Schuchat pointed out the importance for ACIP members to remember that whatever they 

decided to do during this session, they would not get rid of HPV. Additional deliberations and 

WG recommendations are anticipated in October or February regarding the number of doses 

and interval issues. The question of what constitutes revaccination is probably related to what 

constitutes primary vaccination. She appreciated the support for guidance during this transition 

period, with all vaccine products available and the number of people who have received one or 

two doses of what is currently recommended to be a three-dose series. ACIP is likely to be 

asked in the future about alternative intervals, alternative numbers of doses, and possibly 

differences by age. In terms of revaccination, there are many permutations for clinicians to 

absorb. ACIP will have to revisit the topic of HPV vaccination recommendations in the future. 

Lynn Bahta (Minnesota Department of Health) noted that in February 2015, ACIP voted to 

recommend either 2-valent, 4-valent, or 9-valent vaccination. Suddenly, they are now 

concerned that they cannot administer revaccination for 9-valent. That would suggest to 

everyone that they were inadequately vaccinated for 2-valent or 4-valent. That is the indirect 

message in having this conversation. 

Dr. Temte emphasized that ACIP’s current policy does not express a preference. 

Dr. Hahn (CSTE) pointed out that as the parent of an 11-year old girl, she is going to make sure 

that her child receives the 9-valent and feels that they are in an odd position to be talking about 

this conundrum. Few people are starting on the 4-valent based on current recommendations at 

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this point. In terms of the guidance, perhaps a question should be added for naïve persons in 

terms of emphasizing that most young children should be started on the 9-valent vaccine. 

Dr. Markowitz agreed that the transition from 4-valent to 9-valent is a very awkward position to 

be in, and not all providers have 9-valent vaccine. The transition is not going to be immediate. 

The program has been leery to tell providers to delay vaccination. The way to solve this is to 

get 9-valent vaccine into offices quickly to make sure that it is available. 

Dr. Hahn (CSTE) noted that with influenza vaccine, language was used to say that if an office 

had both, one should be used preferentially in certain situations. Perhaps this would be a way 

to address the transition. 

Dr. Lett (Massachusetts) indicated that Massachusetts made a quick transition, and she heard 

that there was ample 9-valent vaccine available for ordering. She requested that the 

manufacturers offer clarification about that. 

Dr. Campos-Outcalt added that this occurred previously with the transition from PCV7 to 

PCV13, in which case, the manufacturer agreed to exchange the vaccines. He wondered 

whether that same arrangement had been made with regard to HPV vaccine. 

Kathy Garrett (Merck) indicated that Merck has no current supply issues, so the vaccine is 

available. They do not have an exchange program available at this time. 

Dr. Schaffner (NFID) asked why there is no exchange program available. 

Kathy Garrett (Merck) responded that Merck’s expectation is that since there is not currently an 

indication for males above the age of 15, the 4-valent vaccine can be used to begin or complete 

the series among males. 

Regarding modeling, Dr. Riley wondered what would happen to the 3000 cervical cancers if 

primary vaccination of a greater percentage of the population was more successful. 

Dr. Chesson responded that they could assess different scenarios of routine vaccination 

coverage and additional vaccination coverage to explore the trade-offs and implications for 

cervical and other cancers. 

It did not seem to Dr. Harriman that one negated the other. Everybody’s efforts could still go 

into getting people vaccinated with the primary series, and those interested in being 

revaccinated could be. To her, it did not seem that one would supplant or affect that other. 

Dr. Schuchat clarified that 3000 cervical cancers were not among those who had received three 

doses of quadrivalent 20 years earlier. That is the total universe, and she did not think that was 

a number on which to focus. 

Dr. Kempe thought there were some issues regarding how making a Category B 

recommendation could affect the receipt of 9-valent vaccine among those who are 

unimmunized. It is likely to send an important message to programs and physicians that it 

becomes much more of a priority to revaccinate with the 9-valent vaccine. It really comes down 

to coverage. The guidelines already say that it is beneficial and that practitioners should use 

individual discretion, but the issue is to ensure that there is not inequity in coverage. There is 

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reason to think that a Category B recommendation does affect the way physicians, 

organizations, and system will deliver the program. 

Dr. Belongia thought the issue regarded whether equity could come at the expense of the 

potential for a Category B recommendation to lead to more of a focus on additional vaccinations 

of people who have already completed a primary series beyond what ACIP intended, rather 

than vaccination of people who need the primary series. 

Dr. Temte said he heard a lot of interest from the liaisons in the possibility of a Category B 

recommendation, and it was somewhat more equivocal among the ACIP members. He 

suggested that this go back to the HPV WG for further consideration at this point. 

Dr. Bocchini said he thought the WG would be happy to provide additional information and work 

through the pros and cons of a Category B recommendation, so that all of the data would be 

before the ACIP to help make that decision. 

Dr. Temte stressed that the intent was to provide the guidance on the website in the interim for 

clinicians. He thought that the strong message should be to emphasize that the important thing 

is initial use of one of the three vaccines and expanding coverage, as that is where the true 

benefit lies. 

Dr. Schuchat pointed out that if this was going to be taken back to the WG, the WG probably 

also needed to reassess what should be done about preference among the licensed products. 

Dr. Markowitz indicated that they would move forward with putting the guidance on the website, 

and taking these issues back to the WG. 

Pertussis 

Introduction 

Art Reingold, MD 

Chair, ACIP Pertussis Vaccine Work Group 

Dr. Reingold reminded everyone that the terms of reference for the Pertussis Vaccine WG are 

to: 

 Review existing statements on infants and young children (1997), adolescent (2006), adults 

(2006), and pregnant and postpartum women and their infants (2008) and consolidate them 

into a single statement. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

 Review new data on Tdap including 

 Effectiveness of ACIP recommendations 

 Interval between Td booster and Tdap 

 Use of Tdap in adults ages 65 years and older 

 Pregnant and breastfeeding women 

• Use of Tdap 

• Cocooning strategies 

 Vaccinated HCP and need for post-exposure prophylaxis 

 Tdap revaccination 

• Pregnant women 

• Healthcare personnel 

• “Cocooning” 

 Review updated epidemiology of tetanus and diphtheria in the US 

Two Tdap products are licensed in the US, both of which are licensed for single use. GSK’s 

BOOSTRIX® vaccine has an age indication of 10 years and older, while Sanofi Pasteur’s 

ADACELTM vaccine has an age indication of 10 through 64 years of age. The current ACIP 

recommendations is for a single Tdap dose for all persons aged 11 years and older, with 

preferred administration at 11 or 12 years of age. Pregnant women are recommended to 

receive a dose of Tdap with every pregnancy. This is primarily designed to provide protection 

to the newborn baby. A decennial Td booster is recommended for those who have received 1 

Tdap vaccine, and a booster is recommended at 5 years for wound management. Diphtheria, 

tetanus, and acellular pertussis (DTaP) vaccine coverage among children is high and 

adolescent Tdap coverage has greatly improved; however, adult Tdap coverage remained low 

at 14% as of 2012. 

Administering Tdap to pregnant women raises safety concerns. There have been 69 Tdap 

reports in pregnant women to the Vaccine Adverse Event Reporting System (VAERS) since the 

last ACIP update in February 2014. Tdap had been given during the third trimester in 15 of 21 

of the reports with data on gestational age at time of vaccination. The conditions among the 69 

reports included no AE (35), injection site reaction/shoulder or arm pain (19), stillbirth (5), 

systemic reactions (3), Guillain-Barré Syndrome (GBS) (2), anaphylaxis allergic reaction (2), 

abdominal pain (1), multiple allergies (1), contractions/unspecified (1). No safety signals have 

been identified in ongoing monitoring. There was a presentation during a prior ACIP meeting 

concerning a possible relationship between Tdap vaccination and an increased risk 

chorioamnionitis. Additional analyses are in progress concerning chorioamnionitis, and there is 

a Clinical Immunization Safety Assessment (CISA) Project underway that is a prospective 

observational clinical study of Tdap safety in pregnant women (ClinicalTrials.gov 

NCT02209623). 

In June 2013, ACIP concluded that the public health impact of routinely recommending a 

second dose of Tdap would be limited, and that no change should be made to the current Tdap 

recommendation. ACIP recognized that the focus should be on preventing pertussis in infants, 

and ensuring that pregnant women receive Tdap during each pregnancy. ACIP supported the 

WG to consider additional doses for special populations, including HCP and close contacts of 

infants. In October 2014, ACIP concluded that there is no supportive evidence to suggest that 

additional doses would be beneficial in prevention of disease and transmission in a health-care 

setting and no change was made to the current ACIP Tdap recommendation for HCP. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

This session included presentations on Cocooning and Tdap vaccination, and acellular 

pertussis vaccine effectiveness among children and adolescents in the setting of pertactindeficient B. pertussis in Vermont from 2011 through 2013. 

“Cocooning” and Tdap Vaccination 

Jennifer L. Liang, DVM, MPVM

National Center for Immunization and Respiratory Diseases 

Centers for Disease Control and Prevention 

As Dr. Reingold noted, Dr. Liang reminded everyone that ACIP made considerations for a 

second dose of Tdap for the general population and healthcare personnel (HCP) but did not 

change the current recommendations. The WG has since considered Tdap vaccination of close 

contacts of infants, and evaluated the need for and potential benefit and impact of additional 

doses. During this session, Dr. Liang presented a summary of these data and the WG’s 

conclusions. The following information was presented to ACIP in October 2014 when reviewing 

considerations for HCP. As a reminder, currently both Tdap vaccines are licensed only for a 

single dose. 

A second dose of Tdap is safe and immunogenic. There are several published clinical trials 

from other countries on a second dose of Tdap at 5 or 10 year after the first dose. Reported 

AEs were generally comparable to those after the first Tdap. The majority of local and systemic 

AEs were mild to moderate and self-limited. Of the few SAEs reported, none were determined 

to be related to receipt of the second Tdap. Safety profiles were comparable at the 5- and 10­

year intervals. For immunogenicity, after a second Tdap, tetanus and diphtheria seroprotection 

were close to 100%. For pertussis vaccine components, responses are similar at the 5- and 10­

year intervals. Responses are also comparable to historic and contemporaneous first dose 

[Halperin 2011; Knuf 2010; Booy 2010, Halperin 2012, Mertsola 2010]. 

In the US, both pharmaceutical companies are conducting clinical trials of a second dose of 

Tdap. Sanofi Pasteur’s US study for a second dose of ADACELTM is complete and was 

presented to ACIP in 2013. A revaccination study in Canada will finish later this year and 

Sanofi Pasteur plans to submit the results to the FDA for consideration of label updates. GSK 

is conducting clinical studies in the US for revaccination after prior vaccination with 

BOOSTRIX®. GSK recently completed a revaccination study of young adults 20 through 28 

years of age who were initially vaccinated 10 years earlier when they were adolescents 11 

through 18 years of age. A revaccination study in adults 28 through 73 years old who were 

initially vaccinated approximately 9 years ago, when they were 19 through 64 years old, began 

this year. Plans to submit the data to the FDA for consideration of a label update for 

BOOSTRIX® will be dependent on pertussis epidemiology and ACIP recommendations. 

With regard to Tdap vaccine effectiveness, previous estimates range between 66% and 78%. 

However, these studies involved adolescents who received some whole cell vaccines as part of 

their childhood series. At the time, the effectiveness of Tdap among adolescents who had 

received only acellular vaccines in childhood was unknown. In 2012, in collaboration with 

Washington State Department of Health, CDC conducted a large-scale study in adolescents 

who only received acellular pertussis vaccines as part of their childhood series. Estimated 

Tdap vaccine effectiveness was 65% and is consistent with previous studies. This study also 

assessed the duration of protection [Rank C, et al. Pediatr Infect Dis J. 2009 28(2):152-3; Wei 

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SC, et al. CID 2010 51(3):315-321; Skoff et al. NIC 2011, Washington, DC; Acosta A, et al. 

Pediatrics 2015 135(6)]. 

In 2012, Wisconsin also evaluated Tdap vaccine effectiveness and duration of protection in 

their adolescent population who received only acellular vaccines. Despite different 

methodologies, both studies showed Tdap to be effective, but that effectiveness decreases with 

increasing time since receipt [1

Acosta et al. Tdap Vaccine Effectiveness and Duration of 

Protection Among Adolescents During the 2012 Washington State Pertussis Epidemic. 

Pediatrics 2015 135(6); 2

Koepke et al. Estimating the Effectiveness of Tdap Vaccine for 

Preventing Pertussis: Evidence of Rapidly Waning Immunity and Differences in Effectiveness 

by Tdap Brand. The Journal of Infectious Diseases 2014]. 

For indirect protection, it is unclear what the effect of Tdap vaccination is on preventing 

pertussis transmission. For people vaccinated with acellular pertussis vaccines, symptoms are 

not as severe and are presumably less likely to transmit. An Australian cocooning case-control 

study found a modest decrease in the risk of pertussis in infants whose parents were 

vaccinated at a sufficient time to boost their immune response relative to the infant pertussis 

incubation period. This effect was also seen in infants whose mothers were vaccinated postpartum. But it is unclear whether the lower risk for infants was attributable to a short-term 

impact on transmission for recently vaccinated mothers or lack of exposure. An animal model 

showed that acellular pertussis vaccinated baboons were protected against disease but not 

infection. Bacterial colony counts from nasopharyngeal washes were comparable to those 

observed in unvaccinated animals. Infected but asymptomatic baboons transmitted pertussis to 

other cohoused baboons. Although these results are striking, it is unclear if this animal model 

represents what happens with humans, vaccines, and infection. There is currently no human 

challenge model [1

Quinn HE et al. Parental Tdap boosters and infant pertussis: a case-control 

study. Pediatrics. 2014 Oct;134(4):713-20; 2

Warfel JM et al. Acellular pertussis vaccines protect 

against disease but fail to prevent infection and transmission in a nonhuman primate model. 

2014 Jan 14;111(2):787-92]. 

Compared with other age groups, infants less than one year of age have the highest reported 

incidence of pertussis compared to other age groups, with incidence ranging from 27 to 127 

cases per 100,000. Young infants have serious pertussis-related complications. Among all 

infant pertussis cases, infants 2 months of age or younger have the highest reported percent of 

hospitalizations and deaths [2014 data are provisional and subject to change; Source: CDC, 

National Notifiable Diseases Surveillance System and Supplemental Pertussis Surveillance 

System]. 

When Tdap was first recommended in 2005, ACIP recommended a dose of Tdap for close 

contacts of infants. This “cocooning” strategy would protect the vaccinated individual from 

pertussis and potentially provide indirect protection to the infant. Ideally, contacts would be 

vaccinated at least 2 weeks before contact with the infant, and pregnant women who had never 

received Tdap would be vaccinated immediately post-partum. This new strategy required a 

shift in thinking and a new paradigm for vaccine delivery. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

In 2010, the US experienced a resurgence of pertussis. California declared an epidemic and 

recommended a dose of Tdap for pregnant women. During this time, ACIP recognized the 

difficulty in widely implementing cocooning programs and considered shifting the timing of the 

mother’s Tdap dose from postpartum to during pregnancy, which would provide earlier direct 

benefit to mother and potentially indirect protection to the infant, and high levels of 

transplacental maternal antibodies would likely provide direct immunity to infants. 

In 2011, ACIP recommended Tdap during pregnancy for women who previously had not 

received Tdap, and if not vaccinated during pregnancy, then a woman was recommended Tdap 

postpartum. In 2012, ACIP expanded the recommendation to every pregnancy, irrespective of 

the patient’s prior history of receiving Tdap. The recommendation for the postpartum dose did 

not change and, therefore, limited the postpartum dose to women who had not previously 

received Tdap. For cocooning, guidance on additional Tdap doses for close contacts including 

the postpartum dose will be forthcoming. 

Successful demonstration cocooning programs have been documented. Programs have been 

primarily hospital-based and targeting the postpartum period. To achieve operational success, 

common strategies were implemented. For the postpartum dose, standing-orders were in 

place. For close contacts, hospitals had on-site clinics with convenient hours and offered free 

Tdap [Yeh S, Mink C, Kim M, Naylor S, Zangwill KM, Allred NJ. Effectiveness of hospital-based 

postpartum procedures on pertussis vaccination among postpartum women. Am J Obstet 

Gynecol. 2014 Mar;210(3):237.e1-6; Wiley KE, Zuo Y, Macartney KK, McIntyre PB. Sources of 

pertussis infection in young infants: a review of key evidence informing targeting of the cocoon 

strategy. Vaccine. 2013 Jan 11;31(4):618-25; Rosenblum E, McBane S, Wang W, Sawyer M. 

Protecting newborns by immunizing family members in a hospital-based vaccine clinic: a 

successful Tdap cocooning program during the 2010 California pertussis epidemic. Public 

Health Rep. 2014 May;129(3):245-51]. 

Despite these successes, cocooning has not been implemented at the national level. The 

challenges programs face are particular to vaccinating close contacts. Logistically, programs 

are targeting close contacts during a short period of time—the postpartum hospital stay. This 

may require additional staffing for education and vaccine administration. There is the inability to 

verify a person’s vaccine history, and not all hospitals are set up to treat outpatients and instead 

may refer family members elsewhere. Financially, there are operational costs to maintaining a 

program. Programs with free vaccine are challenged to ensure continued funding to offer free 

vaccine. For programs that do not offer free vaccine, the hospital faces billing and 

reimbursement challenges. These challenges make it difficult to sustain a program [Healy CM, 

Rench MA, Baker CJ. Implementation of cocooning against pertussis in a high-risk population. 

Clin Infect Dis. 2011 Jan 15;52(2):157-62; Wiley KE, et al. Sources of pertussis infection in 

young infants: a review of key evidence informing targeting of the cocoon strategy. Vaccine. 

2013 Jan 11;31(4):618-25; Rosenblum E, et al. Protecting newborns by immunizing family 

members in a hospital-based vaccine clinic: a successful Tdap cocooning program during the 

2010 California pertussis epidemic. Public Health Rep. 2014 May;129(3):245-51; Healy CM, et 

al. Evaluation of the Impact of a Pertussis Cocooning Program on Infant Pertussis Infection. 

Pediatr Infect Dis J. 2015 Jan; 34 (1):22-26]. 

In 2012, Tdap coverage was 26% in adults who reported living with an infant aged <1 year, but 

it is unclear how complete a cocoon is around an infant. Published reports from cocooning 

programs have reported Tdap uptake highest in postpartum mothers, with limited success in 

vaccinating fathers or other family members. Tdap uptake has been limited by the knowledge 

gap about pertussis and the vaccine, household size impacting the ability to vaccinate all 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

members, and locating where to get vaccinated if no on-site clinic is available [CDC. Urwyler P, 

Heininger U. Protecting newborns from pertussis - the challenge of complete cocooning. BMC 

Infect Dis. 2014 Jul 17; 14(1):397; Rosenblum E, et al. Protecting newborns by immunizing 

family members in a hospital-based vaccine clinic: a successful Tdap cocooning program during 

the 2010 California pertussis epidemic. Public Health Rep. 2014 May;129(3):245-51; Carrico 

CA, O'Keefe C. Protecting infants against pertussis: the cocooning strategy in practice. Nurse 

Pract. 2013 Mar 10;38(3):40-5; Mills B et al. Pharmacist-led Tdap vaccination of close contacts 

of neonates in a women's hospital. Vaccine. 2014 Jan 16;32(4):521-5; Healy CM, Rench MA, 

Baker CJ. Implementation of cocooning against pertussis in a high-risk population. Clin Infect 

Dis. 2011 Jan 15;52(2):157-62; influenza Vaccination Coverage Among Adults — United 

States, 2012. MMWR. 63(05); 95-102]. 

For women who receive Tdap postpartum, the limited evidence on the effectiveness of the 

postpartum dose in preventing infant pertussis is conflicting. A California ecological study noted 

that pertussis incidence in infants born in hospitals with a postpartum Tdap policy was lower 

compared to hospitals without a policy, suggesting that vaccinating new mothers may protect 

infants from pertussis1

. Another study compared the pre-intervention to the post-intervention 

period and found no impact of postpartum Tdap on infant disease2 [

1 Winter K, et al. 

Effectiveness of postpartum Tdap vaccination in California hospitals. CSTE, Portland Oregon. 

Presented June 2010; 2 Castagnini LA, Healy CM, Rench MA, Wootton SH, Munoz FM, Baker 

CJ. Impact of maternal postpartum tetanus and diphtheria toxoids and acellular pertussis 

immunization on infant pertussis infection. Clin Infect Dis. 2012 Jan;54(1):78-84]. 

The evidence on the effectiveness of cocooning in preventing infant pertussis is unclear and 

inconclusive. The WG is aware of two US studies that have attempted to evaluate the impact of 

cocooning: 1) A hospital-based program observed no impact in reduction of infant pertussis, 

but due to the limitations of the study, results should be interpreted with caution; and 2) An 

Emerging Infections Program (EIP) study set out to conduct a case-control study to measure 

effectiveness of cocooning at preventing pertussis among infants <2 months of age. But with 

limited numbers, the study instead assessed the completeness of cocooning. Among infant 

cases and controls, a total of 199 cocoons were identified. Among those, only 9 were fully 

vaccinated cocoons, five of whom for which the mother was the only cocoon member. The 

Australian cocooning case-control study found moderate reduction in risk of pertussis in infants 

whose parents were vaccinated at a sufficient time to boost their immune response relative to 

the infant pertussis incubation period [Healy CM, et al. Evaluation of the Impact of a Pertussis 

Cocooning Program on Infant Pertussis Infection. Pediatr Infect Dis J. 2015 Jan; 34 (1):22-26.; 

CDC, unpublished; Quinn HE et al. Parental Tdap boosters and infant pertussis: a case-control 

study. Pediatrics. 2014 Oct; 134(4):713-20]. 

Over the past decade, with the changing pertussis epidemiology, a shift in the source of 

pertussis transmission to infants has been observed. Previously, parents were commonly 

identified as a source of pertussis, with mothers most often identified. More recently though, 

siblings have been identified as the most common source. Through enhanced surveillance 

data over 8 years in the US, among infant pertussis cases, 44% identified a source of infection. 

Of those, 66% to 85% were classified as family members, with siblings as the most commonly 

identified family member [Wendelboe AM, et al. Transmission of Bordetella pertussis to Young 

Infants. Pediatr Infect Dis J 2007;26: 293–299; Bisgard KM, et al. Infant pertussis: who was the 

source? Pediatr Infect Dis J 2004; 23(11):985-989; de Greeff SC, et al. Pertussis disease 

burden in the household: how to protect young infants. Clin Infect Dis. 2010 May 15; 

50(10):1339-45; Jardine A, et al. Who gives pertussis to infants? Source of infection for 

laboratory confirmed cases less than 12 months of age during an epidemic, Sydney, 2009. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Commun Dis Intell, 2010. 34(2):116-21; Wiley KE, et al. Sources of pertussis infection in young 

infants: a review of key evidence informing targeting of the cocoon strategy. Vaccine. 2013 Jan 

11;31(4):618-25; Bertilone C, et al. Finding the 'who' in whooping cough: vaccinated siblings are 

important pertussis sources in infants 6 months of age and under. Commun Dis Intell Q Rep. 

2014 Sep 30;38(3):E195-200]. 

Since 2011, ACIP has recommended Tdap vaccination for women during pregnancy. Safety 

data continue to be reassuring for both women and newborns. In 2012, the UK recommended 

pertussis vaccination for pregnant women. Two recent publications from the same 

immunization program show agreement of high effectiveness of maternal pertussis vaccination. 

An observational study used the vaccine screening method. For infants less than 3 months of 

age at onset of pertussis, vaccine effectiveness was 91% for infants whose mothers were 

vaccinated at least 28 days before birth. In contrast, effectiveness was 38% for infants whose 

mothers were vaccinated 0 to 6 days before or 1 to 13 days after birth. A case-control study 

assessed the effectiveness in infants <2 months of age at onset of pertussis infection. The 

unadjusted vaccine effectiveness was 91%. When adjusted, the vaccine effectiveness was 

93%. The UK was able to achieve high uptake of pertussis vaccine in pregnant women in a 

short period of time, which allowed for these evaluations [Amirthalingam G, et al. Effectiveness 

of maternal pertussis vaccination in England: an observational study. Lancet. 2014 Oct 

25;384(9953):1521-8; Dabrera G, et al. A case-control study to estimate the effectiveness of 

maternal pertussis vaccination in protecting newborn infants in England and Wales, 2012-2013. 

Clin Infect Dis. 2015 Feb 1;60(3):333-7]. 

Uptake of Tdap among pregnant women has not been as successful in the US. Tdap coverage 

estimates among pregnant women ranges from 14% to 23% [Kharbanda EO, et al. Receipt of 

pertussis vaccine during pregnancy across 7 Vaccine Safety Datalink Sites. Prev Med. 2014 

Oct;67:316-9; Housey M et al. Vaccination with tetanus, diphtheria, and acellular pertussis 

vaccine of pregnant women enrolled in Medicaid--Michigan, 2011-2013 MMWR Morb Mortal 

Wkly Rep. 2014 Sep 26;63(38):839-42; CDC. Internet Panel Survey. Women aged 18–49 years 

pregnant at any time since August of prior year (e.g. 2014 for the April 2015 survey) were 

recruited in a general population internet panel operated by Survey Sampling International]. 

After much discussion, the WG has made the following assessments regarding pertussis and 

vaccinating close contacts of infants with Tdap. The WG recognizes the importance of 

optimizing strategies for preventing pertussis in infants and that many health-care programs 

have put a lot of time and effort into cocooning programs. But after 10 years, implementation 

and sustainability remain a challenge, with barriers preventing close contacts from getting 

vaccinated. There is a lack of data evaluating the effectiveness and impact of this strategy on 

preventing infant pertussis, and the evidence is inconclusive that additional doses for close 

contacts (including the post-partum dose) would be beneficial in prevention of disease and 

transmission of pertussis to infants. Even if additional Tdap doses are recommended, this 

would not address the observed shift to siblings as a source of pertussis transmission to infants 

and puts greater emphasis on the importance of providing newborns with anti-pertussis 

maternal antibodies. There is an optimal strategy in place, vaccinating women during 

pregnancy. 

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At this time, the ACIP Pertussis Vaccines WG concluded that the available evidence does not 

support changes to the current ACIP Tdap recommendation for close contacts of infants, 

including the postpartum dose for women. If Tdap vaccines are licensed for additional doses, 

the ACIP will be asked to reconsider the various policy options. Until then, the focus should be 

on the current pertussis vaccination program, which is to maintain high levels of DTaP 

coverage, sustain Tdap coverage in adolescents, improve adult coverage, and vaccinate 

women during pregnancy to protect infants. 

In an effort to improve Tdap coverage in pregnant women, CDC recently launched a new 

campaign to promote Tdap immunization during pregnancy. After conducting mixed methods 

formative research, new materials targeting pregnant women and prenatal healthcare 

professionals were developed in collaboration with co-branding partners AAFP, AAP, ACNM, 

and ACOG. These are samples of the materials for healthcare professionals: 

Dr. Liang pointed out the emphasis on not relying on postpartum immunization in the first fact 

sheet, and that since reimbursement challenges are a perceived barrier for stocking Tdap, 

ACOG’s reimbursement tools are highlighted an entire sheet was created pertaining to how to 

make a strong referral. 

These are examples of the English and Spanish-language tools for pregnant women. 

Fortunately, the focus groups revealed that pregnant women are very receptive to getting Tdap 

once they learn how it can benefit the baby. A strong recommendation from their provider can 

make all the difference: 

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Discussion Points 

Dr. Temte shared a comment by Dr. Robert Benjamin from Marin County Public Health 

Department in California so that the workgroup would have this information as they move 

forward, “Is pertussis elimination and control a national priority? Will the government incentivize 

the development of a new more immunogenic vaccine?” 

Dr. Reingold responded that the WG has attempted to ascertain what type of pertussis vaccines 

may be under development. The news is not encouraging and better vaccinations are not 

anticipated in the next few years, so Dr. Benjamin’s point is well-taken. 

Ms. Pellegrini asked whether there had been any attempt in the sibling studies to ascertain 

whether siblings were current on their pertussis vaccinations. 

Dr. Liang replied that in that assessment, it was not assessed. 

Dr. Bennett inquired as to whether there was any sense of the age distribution among the 

siblings. 

Dr. Liang indicated that the siblings in the study ranged from 1 to 19 years of age, with a 

median age of about 8 years. 

Dr. Ault (ACOG) conveyed his and Ms. Hayes’ compliments to CDC on the materials for 

practitioners and pregnant women. He noted that ACOG made its recommendation for 

vaccination during pregnancy in the Spring of 2013, and he wondered whether there were any 

data from 2014 and/or 2015 regarding uptake since that recommendation. 

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Dr. Liang replied that the most recent information available is from the Influenza Internet Panel 

Survey of Pregnant Women, which was for the 2014-2015 influenza season. Coverage among 

women during that time period was 23%. The WG is aware that some of the coverage data are 

for a period of time during the transition from 1 dose to a dose during every pregnancy. 

Dr. Plotkin (Vaccine Consultant) said he would like to see more emphasis placed on the timing 

of vaccination during pregnancy. One of the slides indicated up to 36 weeks. There are data 

suggesting that the optimal time for vaccination during pregnancy is between 27 and 30 weeks, 

though these data need to be confirmed. The British data also suggest that vaccinating late in 

pregnancy does not permit time for transplacental passage of antibodies. Therefore, he 

suggested placing more emphasis on timing the vaccination earlier in the third trimester rather 

than at the last moment during pregnancy. 

Regarding coverage, Dr. Sawyer (PIDS) emphasized Dr. Liang’s point that a strong 

recommendation from a provider does resonate well with pregnant women. This is illustrated 

by an effort in the Northern California Kaiser Program that achieved greater than 80% coverage 

for the last three quarters in their pregnant women. 

From a local public health standpoint, Dr. Zahn (NACCHO) the general pushback from local 

obstetricians has pertained to the vaccination not fitting into their clinical model rather than lack 

of knowledge. While exhortation and reminding people of the importance of the vaccines are 

essential, logistically speaking, the reason Kaiser does well with uptake is because there is a 

place where pregnant women can go to be vaccinated. Pharmacies are not a good option due 

to insurance issues and barriers. At the local level, he would like to have more clarity on what 

direction to take beyond posters in terms of where women can be vaccinated consistently. 

Dr. Harriman agreed that while a strong recommendation is great, having the vaccine on site is 

critical so that women can be vaccinated immediately. Even if there are no barriers with 

insurance at a pharmacy, the issue is getting to a pharmacy. It is known from influenza in many 

studies that anything that requires harder work to do, life gets in the way and it does not 

happen. The barriers identified in the ACOG and other studies for prenatal care providers not 

offering vaccines on-site is either real or perceived financial barriers to setting up a program 

and/or not being reimbursed adequately. California has a half a million births per year, 50% of 

which are on Medi-Cal. There are plans to assess uptake within Medi-Cal to determine what is 

occurring. 

Following up on Dr. Harriman’s point, Dr. Temte asked whether there were any data assessing 

family practices that provide obstetrical care versus obstetrical practices per se. His clinic does 

very well with Tdap and pregnancy, with 80% to 90% of pregnant women receiving the vaccine. 

However, they do maintain vaccines on-site. 

Regarding Dr. Plotkin’s comments, Dr. Baker (IDSA) indicated that through CDC funding, one of 

her colleagues is currently running samples. So, there soon will be precise data with these 

vaccines of the timing by week in gestation and the amount of antibody transfer. Another study 

will assess timing at 32 to 34. She works in a hospital in which the pediatric department runs 

the obstetric service, with a group of academic practitioners and a group of private practitioners 

who have offices in the same building with the same pharmacy. There is no barrier of access, 

but there is tremendous disparity even though both groups have been educated. The Baylor 

Academic group has initiated best practices making this part of the EMR. She agreed with Dr. 

Harriman that having vaccine available on site is important, but there must also be 

recommendations by practitioners. 

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Dr. Riley noted that California is at 89% of pregnant women receiving the vaccine and has been 

for a long time, so she is disturbed when she sees the numbers at 22%. She asked where they 

will get the data and whether they will be available moving forward. 

Dr. Liang replied that CDC collects data through the Influenza Internet Panel Survey of 

Pregnant women, which is seasonal for each influenza season, and through the Pregnancy 

Risk Assessment Monitoring System (PRAMS). There is a PRAMS module in which Tdap 

coverage among pregnant women is asked about, but that is an optional module. That is, it is 

not required by all states to choose that set of questions to answer. The last she was aware, at 

least 13 states have been completing the Tdap coverage module. 

Dr. Riley wondered whether a request could be made for mandatory reporting by states of this 

information. 

From a local public health standpoint, Dr. Zahn (NACCHO) reported that far more pertussis is 

being seen. There have been larger waves of disease, and even when the waves go away, a 

lot of disease is still being observed. Increasingly, local public health is emphasizing the 

importance of identifying high risk scenarios (i.e., infants). Nurses in public health always ask 

him about 28 year old dads with infants who should have received Tdap at 23. While every 

adult is supposed to be getting Tdap coverage and data suggests that immunity wanes, there is 

a gap and it is not clear why that 28 person would not be vaccinated. It was not clear to him 

whether this pertained to cocooning or repeat vaccination. This is a logical quandary that 

providers ask him about frequently. 

Dr. Lett said she did not completely understand how PRAMS is operated and funded, she also 

made a plea for the Tdap to be part of the core questions. She learned by chance that it was 

being drafted, and she had to submit a brief and give a presentation to get it included. A board 

within her state had to approve it, and then she had to provide the funding from her program to 

keep the question in. Perhaps CDC could make this part of the core funded questions. 

Acellular Pertussis Vaccine Effectiveness among Children and

Adolescents in the Setting of Pertactin-Deficient B. Pertussis 

Lucy Breakwell PhD

Epidemic Intelligence Service Officer 

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention 

Dr. Breakwell emphasized that despite high vaccination coverage, there has been a resurgence 

of pertussis disease in the US, with notable peaks in 2005, 2010, and 2012. In recent years, 

reported pertussis has significantly increased and remains elevated compared with the previous 

decades [2014 data are provisional; SOURCE: CDC, National Notifiable Diseases Surveillance 

System and Supplemental Pertussis Surveillance System and 1922-1949, passive reports to 

the Public Health Service]. 

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There are several factors which could be contributing to the resurgence in pertussis disease. 

Surveillance bias is one possible explanation. Increased provider and public awareness and 

improved sensitivity of diagnostic tests, such as PCR, can lead to increased identification and 

reporting of pertussis disease. Waning of immunity may play a role, as it could increase 

susceptibility in individuals as time since their last vaccination increases. 

Recent investigations have shown that vaccine effectiveness (VE) wanes among children 

vaccinated solely with acellular vaccines. In a case-control study conducted in California, VE of 

DTaP among children was 89%. Although VE was excellent within one year of receiving the 

fifth DTaP dose at 98%, protection waned to 71% by 5 years post-vaccination. This result is 

consistent with other published studies [Misegades L et al. JAMA. 2012;308:2126-32]. 

Waning of protection was also observed with Tdap. In Washington and Wisconsin, VE of Tdap, 

estimated by two different methodologies, was 73% to 75% within one year of Tdap vaccination, 

but waned to 34% by 2 years post-vaccination. A further contributing factor to the resurgence 

could be genetic changes in the Bordetella pertussis bacteria. One such example is the recent 

emergence of pertactin-deficient pertussis strains. Pertactin may be involved in bacterial 

adhesion to respiratory tract epithelial cells and in resistance to neutrophil-mediated clearance. 

It is also a component of all acellular vaccines in use in the US. Pertactin-deficient strains have 

been identified in Australia, Finland, France, and Japan. In light of this, Dr. Breakwell’s branch 

evaluated the CDC pertussis isolate collection to determine when pertactin-deficient strains 

emerged in the US and their current national prevalence [1

Lam C et al. Emerg Infect Dis. 2014; 

20:626-33; 2

Barkoff AM et al. Clin Vaccine Immunol. 2012; 19:1703-4; 3Bouchez V et al. 

Vaccine. 2009; 27:6034-41; 4

Miyaji Y et al. PLoS One. 2013; 8:e77165; 5Pawloski LC, et al. 

Clin. Vaccine Immunol. 2014; 21:119-25]. 

A pertactin-deficient strain was first identified in 1994, but not again until 2010 when 14% of all 

isolates lacked pertactin. By 2012, 85% of tested isolates were pertactin-deficient, and 

currently around 80% of tested isolates are pertactin-deficient. Pertactin-deficiency does not 

appear to alter clinical symptoms, but may provide a selective advantage as fully vaccinated 

cases were 4 times more likely to have pertactin-deficient pertussis compared to unvaccinated 

cases. The impact of pertactin-deficiency on VE is unknown [Pawloski LC et al. Clin. Vaccine 

Immunol. 2014; 21:119-25; Martin SW et al. Clin Infect Dis. 2015; 60:223-7]. 

In terms of the first evaluation of pertussis VE among pertactin-deficient pertussis strains, the 

objectives were to estimate VE and duration of protection of the 5-dose DTaP series among 4­

through 10-year olds and Tdap among 11 through 19 years olds; and determine VE for both 

vaccines among laboratory confirmed pertactin-deficient pertussis strains. Vermont was an 

ideal place to conduct the evaluation as it had the second highest pertussis incidence rate in 

2012. The state laboratory cultures all pertussis specimens it receives, which is a necessary 

step to determine pertactin status. Based on this, Vermont had a very high proportion of 

pertactin-deficiency among its tested isolates from 2012 among all ages, at 95%. 

Two matched case-control studies were conducted in Vermont. Cases included all probable 

and confirmed pertussis cases reported during 2011-2013, aged 4 through 10 years for the 

DTaP evaluation and 11 through 19 years for the Tdap evaluation. Controls were randomly 

selected from the same age groups from the primary care home of the case in a 3:1 ratio. 

Cases and controls were matched on primary care home and additionally birth year for the 

Tdap analysis. Demographics and pertussis vaccination history were collected for all cases and 

controls from their medical charts. If necessary, vaccination history was further supplemented 

by parent interviews. Conditional logistic regression was used to calculate odds ratios, 

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Regarding the 5-dose DTaP series evaluation, data were collected on 382 cases and 1113 

controls aged 4 through 10 years. Overall, 31% of cases and 35% of controls were excluded, 

predominantly for having unverified vaccination history, having received less than 5 DTaP 

doses, or having 5 DTaP doses off-schedule. Overall, 263 cases and 726 controls were 

included in the analysis. Of the cases, 71% were confirmed and 29% were probable. Of the 

confirmed cases, 83% were laboratory-confirmed and 17% epi-linked. Cases and controls had 

similar demographics, including sex, ethnicity, race, VFC program eligibility, and insurance 

status. Controls were selected from across the entire age range due to the matching criteria. 

Cases were more likely to be older and unvaccinated. Of the cases, 93% were vaccinated 

compared to 99% of controls. VE of the 5-dose DTaP series was estimated at 84%, with 95% 

confidence intervals ranging between 58% and 94%. The study found that over time, protection 

waned. During the first year after receipt of the 5th dose of DTaP, VE was 90%. By 5 to 7 years 

post-vaccination, VE had fallen to 68%, a reduction of 22%. This result is consistent with the 

other studies mentioned earlier. 

 

 

 

 

Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

accounting for matching factors. VE was calculated by 1 minus the odds ratio multiplied by 

100%. 

Cases were classified according to Vermont Department of Health definitions, based on those 

of the Council of State and Territorial Epidemiologists (CSTE). Persons meeting the clinical 

case definition were considered probable cases. Confirmed cases were culture positive, or met 

the clinical case definition and had a positive PCR test, or met the clinical case definition and 

were epi-linked to a lab-confirmed case. Pertactin-deficient strains were pertussis culture 

positive and confirmed to be pertactin-deficient through molecular testing for specific mutations 

and ELISA for protein expression [Adapted definitions of Council of State and Territorial 

Epidemiologists; pertussis case definitions changed in 2014; Pawloski LC et al. Clin. Vaccine 

Immunol. 2014; 21:119-25; Martin SW et al. Clin Infect Dis. 2015; 60:223-7]. 

Vaccination status was confirmed by review of medical charts or by parent interviews. For a 

participant to be considered vaccinated with the 5-dose DTaP series, doses 1-3 were received 

at less than 1 year of age, dose 4 at 1 to less than 2 years of age, and dose 5 at 4 to less than 

7 years of age. For Tdap, a dose was received at or after 11 years of age. Unvaccinated 

participants were defined as having no pertussis-containing vaccines in their medical chart and 

had parental confirmation of non-receipt. Overall, 850 cases aged 4 through 19 years were 

reported to Vermont Department of Health during 2011-2013. Of these, 73% were reported 

during 2012. Cases came from all 12 public health districts and 91 primary care homes. Data 

were collected for 820 cases (96% of reported cases) and 30 cases were excluded because 

their primary care home was based outside of Vermont, they declined to participate, or there 

was an inability to assign them to a primary care home. 

Regarding the Tdap evaluation, data were collected on 438 cases and 1256 controls aged 11 

through 19 years. Overall, 15% of cases and 13% of controls were excluded, predominantly for 

having unverified vaccination history or for having received Tdap before they were 11 years old. 

Overall, 372 cases and 1090 controls were included. Of the cases, 80% were confirmed, of 

which 90% were lab-confirmed and 10% were epi-linked, and 20% were probable. Cases and 

controls had similar demographics, including sex, ethnicity, race, insurance status and vaccines 

for children program eligibility. As a consequence of the matching criteria, similar numbers of 

cases and controls were included for each age year. Cases were more likely to be 

unvaccinated, with 70% of cases vaccinated compared to 84% of controls. 

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To align these findings with current vaccination recommendations, the Tdap VE analysis was 

restricted to participants who had received only acellular vaccines. Vermont has been a 

universal purchaser of vaccines since 1993. Following review of vaccine distribution data 

provided by the Vermont Department of Health, the assumption was made that whole cell 

vaccines were no longer available after 1997. Therefore, this analysis only included 

participants born after 1997, which would encompass all participants aged 11 through 12 years 

and most participants aged 13 through 15 years. Participants who had received only acellular 

vaccines included 244 cases and 714 controls. Tdap VE was estimated at 70%, with 95% 

confidence intervals ranging between 54% and 81%. As with the DTaP vaccine series, duration 

of protection waned with time. During the first year after receipt of Tdap, VE was 76%. By 2 to 

4 years post-vaccination, VE had fallen to 56%, a reduction of 20%. This result was consistent 

with the other studies mentioned earlier. 

In terms of pertussis VE among pertactin-deficient pertussis strains, pertactin status can be 

determined only with culture isolates. Of cases included in the DTaP evaluation, 59% were 

laboratory-confirmed by PCR or culture, while 75% were laboratory-confirmed for the Tdap 

evaluation. Of those DTaP cases that were laboratory-confirmed, 61% were pertussis culture 

positive. Of those, 90% were tested for pertactin deficiency. Of those tested, 98% were 

pertactin-deficient. Of those Tdap cases that were lab-confirmed, 65% were pertussis culture 

positive and of these 92% were tested for pertactin deficiency. Of those tested, 95% were 

pertactin-deficient. Only a limited number of cases from the DTaP VE analysis were pertactindeficient and met the definition of unvaccinated, preventing the estimation of VE among 

pertactin-deficient strains. Tdap VE among pertactin-deficient strains was evaluated. Overall, 

VE was estimated at 51%, with 95% confidence intervals ranging between 5% and 75%. These 

intervals overlapped with those of previous studies. 

In conclusion, initial VE is high but protection wanes over time for both vaccines. These 

findings are consistent with previous VE estimates. Among pertactin-deficient strains, Tdap VE 

was found to be lower, but confidence intervals overlapped with the overall VE estimate. This 

implies that VE among pertactin-deficient pertussis is similar to previous studies, regardless of 

the prevalence of PRN-deficiency. For example, during the 2010 California outbreak and the 

2012 Washington State outbreak, the proportions of pertactin-deficient strains were estimated 

to be 14% and 76%, respectively. These VE estimates are comparable to those two studies, 

strongly suggesting that pertactin-deficiency does not impact VE for reported pertussis disease. 

Regarding limitations, case-control study designs are commonly susceptible to selection and 

information bias. To mitigate this, cases and controls were matched on primary care home to 

ensure exposure to similar circulating pertussis strains and to limit for provider-associated 

diagnostic and reporting biases. Another limitation in this evaluation was the low proportion of 

unvaccinated participants with confirmed pertactin-status. Since pertactin confirmation was 

only completed on 40% of cases, the tested isolates may not be representative of all circulating 

pertussis strains. In addition, if there is a selective advantage to pertactin-deficiency, more 

pertactin-expressing strains may be expected among unvaccinated cases. By including these 

cases in the analysis, vaccine effectiveness may have been over-estimated. The VE estimates 

also are unlikely to account for mild disease, which may be more prominent among vaccinated 

individuals and less likely to be reported. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

These evaluations suggest that the lack of pertactin among currently circulating strains of 

pertussis does not substantially impact VE for reported pertussis disease. However, these 

evaluations did not capture mild or asymptomatic cases and were not able to investigate the 

impact of pertactin-deficiency on transmission. Given that pertactin-deficiency may potentially 

provide a selective advantage, further investigations are required to better define the role of 

pertactin in pathogenesis or transmission. 

Herpes Zoster 

Introduction 

Edward Belongia, MD

Chair, ACIP Herpes Zoster Work Group 

Dr. Belongia reminded everyone that in 2006, the FDA licensed a live attenuated zoster 

vaccine. In 2008, ACIP recommended routine use of this vaccine for all persons over 60 years 

of age who have no contraindications. In 2011, the FDA approved the vaccine for shingles 

prevention in people 50 through 59 years of age. However, ACIP did not make any changes to 

the age recommendations. 

Since that time, there have been some new developments. GSK has an investigational 

adjuvanted vaccine for zoster prevention in healthy adults > 50 years of age. Merck has an 

investigational vaccine for zoster prevention in immunocompromised individuals. The same 

GSK vaccine is being evaluated for zoster prevention in immunocompromised individuals. 

The WG has been inactive for a period of time. Dr. Belongia recently joined last year when he 

became a new ACIP member. New members have been added with clinical expertise in 

immunocompromised patients. The WG history and recommendations have been reviewed, 

and the WG has heard presentations by manufacturers on herpes zoster (HZ) activities and 

status of vaccines in development. 

During this session, an update was presented on herpes zoster epidemiology and vaccine 

coverage, and results were presented from a Phase 3 efficacy study of adjuvanted zoster 

subunit vaccine in adults ≥ 50 years old. 

Update on Herpes Zoster Epidemiology and Vaccine Uptake 

Rafael Harpaz, MD, MPH 

CDC Lead, Zoster Work Group

National Center for Immunization and Respiratory Diseases

Centers for Disease Control and Prevention 

During this session, Dr. Harpaz discussed the clinical manifestations and epidemiology of HZ, 

the zoster vaccine, recent policy developments, and zoster vaccine uptake. Regarding the 

clinical picture, HZ manifests as a painful unilateral rash. The rash generally affects 1 to 3 

adjacent dermatomes. It develops over approximately 5 to 7 days and generally resolves within 

approximately 25 days. While the rash can at times cause secondary infections or scarring, 

and while it can transmit varicella zoster virus (VZV) to susceptible children to cause 

chickenpox, the primary acute concern regarding HZ is pain, which can at times be 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

excruciating. About 90% of patients with HZ experience pain, or some kind of distressing 

sensation. In fact, these symptoms typically precede the rash by 1 to 5 days or more, which 

can lead to diagnostic dilemmas and work-ups for a cardiac or abdominal etiology, and the 

uncertainty of it all itself causes patients distress. 

However, the most feared complication of HZ is surely post-herpetic neuralgia (PHN). This is 

the prolonged, sometimes incapacitating pain that continues after resolution of the rash. While 

definitions regarding pain duration vary, PHN lasts weeks to months or even years. While 

prompt use of antivirals may relieve the chronic pain of HZ, treatment of HZ is at best only 

partially effective at preventing PHN. Furthermore, while there are guidelines for treatment of 

the PHN itself, these treatments only provide partial and inconsistent benefit. In addition, PHN 

treatments involve psychotropic medications such as opioids, anti-seizure medications, and 

tricyclic antidepressants that are often poorly tolerated and cause serious side effects, 

particularly in the elderly. The underlying pathophysiology of PHN is not known, just as it is not 

known for HZ. PHN is clearly contingent on HZ, but the extent to which the pathways leading to 

HZ and to PHN are distinct is unknown. Another common and important complication of HZ is 

herpes zoster ophthalmicus (HZO), which occurs with involvement of the ophthalmic division of 

trigeminal nerve. HZO can lead to chronic ocular complications, reduced vision, or even 

unilateral blindness. 

It is difficult to discuss the epidemiology of HZ without first discussing its risk factors. There are 

two risk factors that are particularly important. The first of these is age. Age is the dominant 

factor driving incidence and burden of HZ in any population. The rate of HZ really starts to 

increase at the age of 50 years1

. Similar data have been reported in virtually every study on HZ 

ever conducted, regardless of methods. Not only is age the dominant risk factor for HZ, but 

also it is the primary determinant of the severity of that HZ. The impact of age on PHN is even 

greater than that for HZ, being approximately 10 times higher in persons >80 compared to 

those 50 through 59 years of age. In fact, for every 1000 persons with HZ, most severe 

outcomes increase dramatically with age, especially hospitalization. The oldest old have the 

least reserve to tolerate PHN, and have the most difficulty tolerating anti-PHN treatments2 

[

1

Marketscan administrative data, Insinga et al., J Gen Intern Med. 2005, 20:748-53; 2Olmsted 

County, MN, Yawn, et al., Mayo Clin Proc. 2007; 82:1341-9]. 

The second key risk factor for HZ is immunosuppression. While this is less common in the 

population, it remains quite influential due to the magnitude of associated risk. For instance, HZ 

risk is increased up to 50-fold for hematological malignancies, stem cell transplantation, or HIV 

infection. In addition, among those experiencing HZ, it is the immunocompromised patients 

who experience the most serious and even life- or sight-threating complications. 

With that background on risk factors, the annual rate of HZ is approximately 4 per 1000 

population per year in the US, which translates to approximately 1 million cases annually. The 

lifetime risk of developing HZ is thus about 30%. While age and immunocompromize explain a 

large percentage of HZ cases, what distinguishes most of the 30% of persons who develop HZ 

during life from the 70% who do not is inexplicable. Finally, age-adjusted rates appear to be 

increasing. 

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The following graph shows age-stratified Medicare data on HZ incidence among persons 65+ 

on the Y axis, and calendar time from 1992-2010 on the X axis: 

Rates have been increasing substantially over time, for all age groups. This pattern has been 

also observed in other data from the US, dating as far back as the 1940s. Age-specific 

increases have been observed in Canada, East Asia, and elsewhere. There is no cohesive 

explanation for this finding. 

Zostavax® was licensed in 2006 based on the Shingles Prevention Study (SPS). The trial 

involved over 38,000 healthy adults 60 years of age and older who were followed for about 3 

years. Subjects were randomized to receive placebo or the attenuated Oka strain VZV found in 

the varicella vaccine, Varivax®, but at a 14 times or greater titer. Vaccine efficacy was found to 

be 51% for the HZ outcome, and 67% for the PHN outcome. No SAEs were attributed to the 

vaccine, though local reactions were common. Based on these results, ACIP recommended 

routine vaccination of adults of ages 60 and older with a single dose of Zostavax®. Results of 

the SPS have since been supported by observational studies. 

In terms of the results of the SPS focusing on the association of vaccine efficacy as a function 

of age, Dr. Harpaz highlighted two findings. First, VE for HZ drops steeply with age to just 18% 

for persons 80 and older. Secondly, not only is VE for PHN generally better, but also it is 

considerably better preserved as a function of age, with a VE of 39% in persons 80 years of 

age and older. The vaccine works progressively better at averting the most prolonged episodes 

of PHN. It is these longest episodes, some that can extend for many years, that are the most 

critical targets for prevention. 

There have been several more recent developments with policy implications in the zoster arena. 

First, there was a large multinational randomized clinical trial of Zostavax® in persons 50 

through 59 years of age. Follow-up lasted just over a year. The vaccine had a VE against HZ 

of 70%. Based on these results and the associated reassuring safety data, the FDA issued a 

license for Zostavax® among adults 50 through 59 years of age in 2011. Also, subjects from the 

original SPS trial of adults then 60 and older were enrolled into a longer follow-up study that 

extended out approximately 11 years following vaccination. There was no concurrent control 

group since the controls from SPS were all offered Zostavax® after that study was completed. 

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Therefore, the long-term follow-up study was unblinded and less-powered than the SPS. 

Finally, the study relied on historic controls to define protection, but given the rapidly changing 

incidence in HZ over calendar time discussed earlier, it was hard to draw clear conclusions 

about waning of protection from this study. In another development, a clinical trial was 

conducted to compare safety and immunogenicity of a second dose of Zostavax® (booster 

dose) administered to adults 10 years after a first dose, as compared to immunogenicity in age 

matched adults receiving a first dose of the vaccine. The immunogenicity outcomes were 

comparable in 2 study arms, but these immunogenicity outcomes do not adequately predict 

protection to address many key questions. 

With these developments, in October 2013 ACIP reviewed Zostavax® recommendations and left 

them unchanged; that is, a routine recommendation for 1 dose of Zostavax® in adults aged 60 

years and older. This was essentially an example of “programmatic conservatism.” On one 

hand, given uncertainty about waning, a change in recommendation to vaccinate adults at age 

50 might leave them unprotected decades later at ages when the burden of PHN would be 

greatest. But on the other hand, the degree of added protection conferred by a second dose of 

Zostavax® is unknown, regardless of associated added program costs and complexities. In the 

absence of adequate evidence on key issues, it was felt that a major change in the Zostavax® 

program could not be justified, whether to lower the age at vaccination to 50 or to add a second 

dose recommendation. 

Zostavax® uptake among adults 60 years of age and older increased from 1.9% in 2007 to 

approximately 24% in 2013, though more recent data from Merck on doses delivered suggest a 

substantial jump by the end of 2014 to 30%. National data suggest that even with modest 

levels of vaccine uptake, racial and ethnic disparities have been developing. Uptake has been 

sluggish for a number of reasons. First, there is price. At a catalogue price of approximately 

$200, HZV is the most expensive adult vaccine on a per-dose basis. Not only does this make 

the vaccine less cost effective on a societal level, but also it results in high up-front inventory 

costs for providers, placing them at financial risk. There are also the issues of storage and 

handling. In the US, HZV must be stored frozen and is the only freezer-requiring vaccine for 

adults. Many adult providers are not equipped to handle frozen vaccines. Furthermore, in 

context of inventory price, the chances of freezer failure means that providers feel that their 

financial risk is even greater. Merck has a program to share part of that risk, but providers may 

not be aware of that program. 

Between 2007-2011, there were repeated supply shortages due to the challenges of 

manufacturing this very finicky live attenuated vaccine. Merck has done a great job adding 

manufacturing capacity and the problems now seem resolved. However, during that interval, a 

lot of time was lost since there was little promotion of the vaccine. Furthermore, it is likely that 

many physicians and patients became frustrated and lost interest in the vaccine during that 

time. There are also barriers imposed by the Medicare Part D program. In contrast to 

commercial health insurers who are obligated by provisions of the affordable care act to cover 

Zostavax® without any cost sharing by patients, Medicare Part D coverage of Zostavax® 

paradoxically involves large costs by patients, typically in the range of $100. Some patients 

need to pay the full vaccine costs up front, with partial reimbursement weeks after filing. The 

program is also very administratively complex for physicians, though it is fairly seamless for 

pharmacies. ACIP has heard a number of presentations in the past about the growing role of 

pharmacies as vaccination sites. This is a recent development affecting all vaccines, but it has 

had a particular impact on Zostavax® due to pharmacies administering a large percentage of 

the vaccine. This development does, however, mean that systems for tracking doses of adult 

vaccine need to be firmly established. 

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Zostavax® is additionally affected by the same barriers as other adult vaccines and, more 

generally, adult prevention measures. While this is not the forum to inventory all those barriers, 

in general, adult providers must address chronic disease management, acute care needs, and 

administrative burden, leaving them with little time for prevention. Furthermore, adult providers, 

including public health itself, have less of a “prevention mindset” with seniors. Finally, there is a 

general fragmentation of health care for seniors, making accountability for prevention 

challenging. 

Results of GSK Phase 3 Study of Investigational Adjuvant-Based Zoster Vaccine 

Thomas Heineman, MD, PhD 

Director, Clinical Research and Development

GlaxoSmithKline Vaccines 

Dr. Heineman indicated that from the beginning, GSK conceived its zoster vaccine program to 

target two particular high-risk populations, adults 50 years of age and older and 

immunocompromised adults 18 years of age and older. With that in mind, the herpes zoster 

adjuvanted subunit vaccine (HZ/su) candidate vaccine was developed. The HZ/su vaccine was 

specifically designed to elicit strong cellular and humoral immune responses against VZV in 

these high-risk populations who would be anticipated to be somewhat immunologically resistant 

to the vaccination. The HZ/su vaccine contains a vaccine antigen, the purpose of which is to 

target the immune responses of the vaccine to the VZV pathogen. The antigen contained in the 

vaccine is VZV glycoprotein E (gE), which was selected for a number of reasons, but most 

particularly because it is expressed abundantly in the virion envelope of the VZV virus and the 

membranes of VZV-infected cells. Perhaps more importantly, it is a prominent target for VZVspecific cellular and humoral immune responses. In addition to a vaccine that is specific to 

VZV, a vaccine is needed that stimulates an immune response of sufficient magnitude to 

enhance the likelihood of protection. With that in mind, the antigen was combined with one of 

GSK’s proprietary adjuvant systems. In this case, the adjuvant system 01B (AS01B) was 

selected. The GSK proprietary AS01 adjuvant system is a liposome-based adjuvant that 

contains 2 immunostimulants: QS-21 and monophsophoryl lipid A (MPL). This adjuvant is 

designed specifically to enhance both cellular and humoral immune responses to subunit 

antigens, and was shown in a series of pre-clinical studies in small animals that when gE is 

combined with this adjuvant, it elicits robust gE-specific CD4+ T-cell and humoral immune 

responses in mice. 

Subsequent to the completion of the pre-clinical program, GSK moved on to Phase 1 and 2 

clinical trials, all of which have been published. To highlight a few of the key conclusions from 

these studies, two doses of HZ/su vaccine administered at 0 and 2 months induced robust gE

specific CD4+ T cell and humoral immune responses in adults 50 years of age and older. 

These immune responses to the HZ/su vaccine were well-preserved with the subject age, 

including in adults 70 years of age and older. In older adults, immune responses to the HZ/su 

vaccine persisted well over time and remained above baseline for 6 years following vaccination. 

In autologous hematopoietic stem cell transplant (aHCST) recipients and HIV-infected adults, 

two doses of HZ/su vaccine induced immune responses comparable to those in older adults. 

Following a cohort of older adults immunized with the HZ/su vaccine over time, at Month 3 (one 

month after the second dose of vaccine), the cellular immune response peaks at about 19-fold 

over the baseline level—keeping in mind that all of the subjects are VZV seropositive to begin 

with. The cellular immune responses decline over time, as would be expected, but begin to 

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plateau after a couple of years. Thus, at Month 72 or 6 years after the original vaccination, the 

cellular immune responses remains at approximately 4-fold over the baseline level. 

With the Phase 1 and 2 data in hand, GSK moved forward to Phase 3 efficacy studies. The 

highlight of that component of the program are three pivotal efficacy studies, two of which are 

being conducted in older adults (ZOE-50 and ZOE-70). The zoster efficacy (ZOE)-50 study is 

an efficacy study being conducted in adults 50 years of age and above, and ZOE-70 is an 

efficacy study being conducted in adults 70 years and above. These studies have virtually 

identical designs except for the age of the subjects enrolled. The third study, 002, is a true 

efficacy study in aHCST recipients 18 years of age and older. During this session, Dr. 

Heineman presented the efficacy and safety results of ZOE-50 study. Though not presented, 

the following supporting studies are part of the HZ/su Development Program: 

Study Population Objectives Status 

Co-administration studies 

004 ≥50 yoa Influenza vaccine (quadrivalent) Ongoing

035 ≥50 yoa Pneumococcal vaccine (PPV-23) Ongoing 

042 ≥50 yoa Tdap vaccine Ongoing 

Other older adult studies 

007 ≥50 yoa Lot-lot consistency Ongoing 

026 ≥50 yoa Schedule comparison Completed 

033 ≥50 yoa with history of HZ Safety/immunogenicity Completed 

048 ≥65 yoa; prior ZostavaxTM recipients Safety/immunogenicity Planned 

Other studies in immunocompromised populations (≥18 yoa) 

028 ≥18 yoa; solid organ malignancy Safety, immunogenicity Ongoing 

039 ≥18 yoa; hematological malignancy Safety, immunogenicity Ongoing 

041 ≥18 yoa; renal transplant Safety, immunogenicity Ongoing 

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The primary objective of the ZOE-50 study was to evaluate the overall vaccine efficacy in 

reducing HZ risk compared to placebo in adults 50 years of age and older. The secondary 

analysis objectives were to determine vaccine efficacy in reducing HZ risk compared to placebo 

in each age stratum (50 through 59, 60 through 69, and 70+ years); and evaluate HZ/su safety 

and reactogenicity. The secondary protocol-specified objectives to be analyzed upon 

completion of ZOE-50 and ZOE-70 studies included the following: 

VE in reducing PHN 

VE in reducing HZ-associated complications (other than PHN) 

VE in reducing HZ-related mortality and hospitalizations 

VE in reducing HZ-associated pain (acute pain and duration of pain) 

VE in reducing use of pain medications 

VE in improving QoL 

Humoral and cellular immunogenicity 

Note that these very important and interesting secondary objectives that are part of this study 

have not yet been analyzed, given that they will be analyzed at the time the ZOE-70 study is 

completed in order to have maximal power to draw conclusions on the data. 

ZOE-50 was a randomized, observer-blind, placebo-controlled study conducted in 18 countries 

in Asia/Australia, Europe, Latin America, and North America among adults 50 years of age and 

older stratified by age (50 through 59, 60 through 69 and 70+ years). Exclusion criteria 

included individuals with a history of HZ, previous vaccination against VZV or HZ, and 

immunocompromising conditions. The study groups were randomized 1:1 to receive HZ/su 

vaccine or a saline solution placebo. Two doses of HZ/su vaccine or placebo were injected 

intramuscularly at 2-month intervals. Contact included visits at Months 0 and 2 for vaccination 

and at Months 3, 14, 26, and 38. Monthly phone calls were made to subjects for collection of 

safety data and suspected HZ cases. 

Subjects were educated at the beginning of the study and at every opportunity thereafter to 

recognize a suspected case of HZ, which was defined as “new unilateral rash accompanied by 

pain (broadly defined to include allodynia, pruritus or other sensations) and no alternative 

diagnosis.” Subjects with suspected cases meeting this definition were asked to return to their 

study site within 48 hours to be evaluated by the study investigators. If the study investigators 

thought it was clearly not HZ, subjects were sent home. Suspected HZ cases triggered further 

evaluation that included collection of samples from the rash for PCR evaluation, as well as 

digital photographs of the rash. The samples were then tested by quantitative PCR (qPCR) and 

if positive for VZV, the cases were then considered confirmed for HZ. If negative it was 

considered not zoster. Indeterminate results were sent for final case adjudication by the HZ 

Adjudication Committee (HZAC). 

The results of the study were derived by the analysis of three specific cohorts. The first cohort 

was the total vaccinated cohort that included 15,411 subjects who received at least 1 dose of 

vaccine. The mean follow-up time was 3.5 years. This cohort was comprised of 7698 HZ/su 

vaccine recipients and 7713 placebo recipients, and was the primary cohort for the safety 

analyses. The second cohort was the modified total vaccinated cohort (mTVC) that included a 

total of 14,759 subjects, excluding subjects not receiving Dose 2 or who developed HZ within 1 

month after Dose 2. The mean follow-up time was 3.2 years. This cohort was comprised of 

7344 HZ/su vaccine recipients and 7415 placebo recipients, and was the primary cohort for the 

efficacy analyses. There was also a diary card cohort with 8926 subjects from the total cohort 

who were evaluated in more detail for any vaccine reactions. This cohort was comprised of 

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4460 HZ/su vaccine recipients and 4466 placebo recipients, and was the primary cohort for the 

reactogenicity analyses. 

Regarding the demographics of the subjects, the average age of the enrollees was 

approximately 62 years. There was a gender distribution of about 61 females and 39 males. 

Most of the subjects (~70%) were white, with most of the remainder being Asian. 

Approximately half of the subjects were enrolled in Europe and the remaining subjects were 

enrolled in either Asia, Australia, Latin America, or North America. 

In terms of the results for the mTVC, recall that the primary objective was vaccine efficacy in 

subjects 50 years of age and older. Vaccine efficacy in this group was 97.2%, with confidence 

intervals from 93.7% to 99.0%. The efficacy was calculated by comparing the incidence rates in 

the vaccine and placebo groups. The incidence rate was 9.1 zoster cases per 1000 person 

years in the placebo group, and 0.3 zoster cases per 1000 person years in the vaccine group. 

There were 210 HZ cases confirmed in the placebo group and 6 cases confirmed the vaccine 

group. Efficacy for each of the pre-specified age cohorts (50 through 59, 60 through 69, and 

70+ years) was essentially identical to the overall efficacy ranging from 96.5% to almost 98%. 

There was no indication from the study that efficacy declines with the age of the subject at the 

time of initial vaccination. For completeness, efficacy in people 60 years of age and above was 

97.6% or basically in the same range. As noted earlier, the mean follow-up time was 3.2 years 

for these analyses. It is important to note the ZOE-50 study remains blinded at the subject level 

because the study is ongoing. Therefore, to avoid unblinding, vaccine efficacy by year has not 

been communicated to the study team. However, there is no apparent waning of efficacy by 

year during years 1 through 4 of follow-up within this study. The analyses were performed by 

blinded, external statisticians at the group level. Because there are so few breakthrough cases 

of zoster in the vaccine group, the study team cannot be provided with the year-by-year efficacy 

numbers without unblinding at the subject level. 

Safety analyses were performed for SAEs, potential immune mediated diseases (pIMDs), and 

deaths. There was no imbalance in these safety endpoints for the vaccine and placebo groups 

when considered for the duration of the study, or during the 30 days immediately following 

vaccination. In terms of solicited local symptoms (pain, redness, swelling) reported during the 7 

days post-vaccination, approximately 80% of the vaccine group experienced some type of 

symptom compared to about 12% in the placebo. The most common local adverse event was 

pain. Of these, about 9.5% of the vaccine group had Grade 3 pain as compared to 0.4% of the 

placebo group. The median duration of local symptoms overall was 3 days. The median 

duration of Grade 3 symptoms was 1 day for pain and 2 days for redness and swelling. For 

solicited general symptoms reported during the 7 days post-vaccination, approximately twothirds of subjects had some general reaction during the course of the study, with slightly less 

than one-third in the placebo group having some reaction. The most common reactions in the 

vaccine group were myalgia, fatigue, and headache. The median duration of general reactions 

was 2 days for fatigue, gastrointestinal symptoms, headaches and myalgia and 1 day for fever 

and shivering. The median duration for Grade 3 symptoms, regardless of which category, was 

1 day. 

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To summarize the ZOE-50 results, HZ/su vaccine efficacy was 97.2% for the prevention of HZ 

in adults 50 years of age and older. HZ/su vaccine efficacy appeared to be age-independent 

and fully preserved in people 70 years of age and older. HZ/su vaccine efficacy did not wane 

during the study period. No imbalance was observed in the incidence of safety endpoints 

(SAEs, potential autoimmune diseases, deaths) between the HZ/su vaccine and placebo 

groups. Local and systemic reactions to HZ/su vaccine are common in the first 7 days after 

vaccination, with the large majority being mild to moderate in intensity and short in duration. 

Regarding upcoming results and next steps, as mentioned earlier, results are anticipated in the 

relatively immediate future for the ZOE-70 study and the ZOE-50/ZOE-70 pooled analyses. 

This will provide additional information of VE against HZ in people 70 years of age and older, as 

well as data on VE against PHN, HZ-associated pain, et cetera. The efficacy results are also 

forthcoming from the aHCST study and several ongoing supporting studies (e.g., coadministration studies, safety/immunogenicity in immunocompromised populations, et cetera). 

In addition to those studies, GSK plans to conduct long-term post-vaccination follow-up with 

vaccine recipients to assess duration of protection and immune persistence. Other studies will 

be conducted to follow-up on earlier studies for long-term immunogenicity outcomes. In the 

near future, the boostability of the vaccine will be assessed at remote times following the initial 

course. Additional studies also will be conducted to assess the impact of the vaccineassociated reactogenicity on quality of life (QoL), normal daily activities, et cetera. 

Discussion Points 

Dr. Rubin asked whether AEs were worse following Dose 2 versus Dose 1. Dr. Heineman 

replied that the incidence of AEs did not change from Dose 2 to Dose 1. 

Dr. Romero was struck by the paucity of minority populations in the study, and wondered 

whether GSK had any plans to try to increase those numbers. 

Dr. Heineman responded that the study enrolled approximately 2000 subjects in the US. The 

proportion of minorities enrolled is dependent largely upon study sites, et cetera. Clearly, they 

would like to have more minorities in future studies. 

Dr. Temte asked whether GSK had a projected timeline for submission to FDA. 

Dr. Friedland (GSK) replied that while it was too early to speculate about when the file would be 

submitted, the study reports will be submitted as soon as they are ready for review. 

Dr. Schuchat asked whether Dr. Heineman could comment on plans to assess patients who 

previously received Zostavax®. 

Dr. Heineman responded that GSK does have plans to evaluate the HZ/su vaccine in people 

who previously received Zostavax®. 

Dr. Temte asked whether there were any plans to consider HZ/su vaccine as a pediatric 

vaccine for primary protection from chicken pox. 

Dr. Heineman replied that as of now, GSK has no plans to test HZ/su vaccine as an alternative 

to the currently available vaccines, but it is an interesting question. 

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Dr. Kelly Moore (AIM) noted that though the audience may seem somewhat blasé, they were 

actually thinking, “Wow, that’s really exciting!” 

Dr. Temte asked Dr. Harpaz whether there was any speculation regarding the increase in 

zoster rates over time that he discussed. 

Dr. Harpaz replied that he has given this a lot of thought and has assessed every possibility that 

he has ever considered or heard, and has come up with no cohesive explanations. It does not 

appear to him and others that the increase is associated with the varicella vaccine program as a 

result of declines in exposure to varicella disease with less external immunological boosting, as 

has been speculated by some. In particular, the increase in zoster rates started occurring 

preceding the onset of the varicella vaccine program, and similar increases have been 

observed in several other countries. 

Dr. Reingold pointed out that there is an increasing prevalence of immunocompromising 

conditions that may increase the risk. 

Dr. Harpaz responded that while that was a good point, the studies to which he referred 

controlled for immunocompromised status and chronic disease status. 

Dr. Temte found the results to be very encouraging. He noted that he has seen his practice age 

for over 25 years, with most of his pediatric population being in their 40s. They routinely see 

zoster in older patients, and it has incredible effects on QoL. Having a more affordable vaccine 

would be desirable. In his very ethnically and racially diverse practice, he is always struck that 

virtually all of his elderly patients know about this vaccine. The problem is the ability to pay. 

This is a vaccine for which he is certain there are economic disparities in practices. 

Regarding the graph Dr. Harpaz showed with the increase in incidence, Dr. Schuchat observed 

that the last couple of years appeared to show that incidence was flattening or possibly 

decreasing. She wondered whether that was a significant difference and if thought had been 

given to this. 

Dr. Harpaz replied that this is a fascinating observation that they have been exploring to assess 

where it is going. The plateauing in the oldest population seems to be continuing. It depends 

upon the age group. 

Day 2: Public Comment 

No public comments were offered during this session. 

Dr. Temte thanked everyone for all of their service, wished them safe travel home, and 

concluded the June 2015 meeting with two lines from Shakespeare’s last play: 

As you from crimes would pardoned be, 

Let your indulgence set me free. 

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Certification 

Upon reviewing the foregoing version of the June 24-25, 2015 ACIP meeting minutes, Dr. 

Jonathan Temte, ACIP Chair, certified that to the best of his knowledge, they are accurate and 

complete. His original, signed certification is on file with the Management Analysis and 

Services Office (MASO) of CDC. 

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ACIP Membership Roster 

CHAIR 

TEMTE, Jonathan L., MD, PhD 

Professor of Family Medicine 

University of Wisconsin School of Medicine and Public Health 

Madison, WI 

Term: 07/01/2011-06/30/2015 

EXECUTIVE SECRETARY 

WEINBAUM, Cindy, MD 

Acting Executive Secretary, ACIP / CDC 

Medical Officer, NCEZID / DHQP / OD 

Centers for Disease Control and Prevention 

Atlanta, GA 

MEMBERS 

BENNETT, Nancy, MD, MS 

Professor of Medicine and Community and Preventive Medicine 

University of Rochester School of Medicine and Dentistry 

Rochester, NY 

Term: 07/01/2011-06/30/2015 

BELONGIA, Edward, MD 

Director 

Center for Clinical Epidemiology & Population Health 

Marshfield Clinic Research Foundation 

Marshfield, WI 

Term: 07/01/2014-06/30/2018 

BOCCHINI, Joseph A., Jr., MD 

Professor and Chairman 

Department of Pediatrics 

Louisiana State University Health Sciences Center 

Shreveport, LA 

Term: 07/01/2011-06/30/2015 

CAMPOS-OUTCALT, Douglas, MD, MPA 

Medical Officer 

Mercy Care Plan 

Phoenix, AZ 

Term: 07/01/2011-06/30/2015 

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HARRIMAN, Kathleen, PhD, MPH, RN 

Chief, Vaccine Preventable Disease Epidemiology Section 

Immunization Branch 

California Department of Public Health 

Richmond, CA 

Term: 07/01/2012 – 06/30/2016 

HARRISON, Lee H., MD 

Professor of Medicine and Epidemiology 

Infectious Diseases Epidemiology Research Unit 

University of Pittsburgh 

Pittsburgh, PA 

Term: 07/01/2012 – 06/30/2016 

KARRON, Ruth A., MD 

Professor and Director 

Center for Immunization Research 

Department of International Health 

Johns Hopkins Bloomberg School of Public Health 

Baltimore, MD 

Term: 07/01/2012 – 06/30/2016 

KEMPE, Allison, MD, MPH 

Professor of Pediatrics 

Director of Primary Care Fellowship 

University of Colorado School of Medicine 

Director of Research 

Division of General Academic Pediatrics 

Director of Children’s Outcomes Research Program 

The Children’s Hospital of Denver 

Denver, CO 

Term: 07/01/2013 - 06/30/2017 

PELLEGRINI, Cynthia 

Senior Vice President 

Public Policy and Government Affairs 

March of Dimes 

Washington, DC 

Term: 07/01/2013-06/30/2017 

REINGOLD, Arthur L., MD 

Professor of Epidemiology 

Edward Penhoet Distinguished for Global Health and Infectious Disease 

Associate Dean for Research 

School of Public Health 

University of California 

Berkeley, CA 

Term: 07/01/2013-06/30/2017 

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RILEY, Laura E., MD 

Associate Professor, Obstetrics, Gynecology and Reproductive Medicine 

Harvard Medical School 

Maternal Fetal Medicine 

Massachusetts General Hospital 

Boston, MA 

Term: 07/01/2014-06/30/2018 

ROMERO, José R., MD, FAAP 

Professor of Pediatrics 

Horace C. Cabe Endowed Chair in Infectious Diseases 

Director, Pediatric Infectious Diseases Section 

University of Arkansas for Medical Sciences and 

Arkansas Children's Hospital 

Director, Clinical Trials Research 

Arkansas Children's Hospital Research Institute 

Little Rock, AR 

Term: 07/01/2014-06/30/2018 

RUBIN, Lorry, MD 

Director 

Pediatric Infectious Diseases 

Steven and Alexandra Cohen Children’s Medical Center of New York 

North Shore-Long Island Jewish Health System 

New Hyde Park, NY 

Professor of Pediatrics, Hofstra-North Shore LIJ School of Medicine 

Hempstead, NY 

Term: 07/01/2012 – 06/30/2016 

VÁZQUEZ, Marietta, MD 

Associate Professor of Pediatrics 

Department of Pediatrics 

Yale University School of Medicine 

New Haven, CT 

Term: 07/01/2011-06/30/2015 

EX OFFICIO MEMBERS 

Centers for Medicare and Medicaid Services (CMS) 

HANCE, Mary Beth 

Senior Policy Advisor 

Division of Quality, Evaluations and Health Outcomes 

Children and Adults Health Programs Group 

Center for Medicaid, CHIP and Survey & Certification 

Centers for Medicare and Medicaid Services 

Baltimore, MD 

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Department of Defense (DoD) 

SERGIENKO, Eric, MD, MPH CAPT 

Medical Corps 

United States Navy Department of Defense Liaison Centers for Disease Control and Prevention 

Atlanta, GA 

Department of Veterans Affairs (DVA) 

KINSINGER, Linda S., MD, MPH 

Chief Consultant for Preventive Medicine 

Office of Patient Care Services 

National Center for Health Promotion and Disease Prevention 

Durham, North Carolina 

Food and Drug Administration (FDA) 

SUN, Wellington, MD 

Director, Division of Vaccines and Related Product Applications 

Office of Vaccines Research and Review 

Food and Drug Administration 

Rockville, MD 

Health Resources and Services Administration (HRSA) 

HOUSTON, A. Melissa, MD, MPH, FAAP 

Chief Medical Officer 

Division of Vaccine Injury Compensation 

Health Resources and Services Administration 

Rockville, MD 

Indian Health Service (IHS) 

GROOM, Amy, MPH 

Immunization Program Manager 

Indian Health Service 

Albuquerque, NM 

National Vaccine Program Office (NVPO) 

GELLIN, Bruce, MD, MPH 

Director 

National Vaccine Program Office 

Department of HHS, Public Health and Science 

Washington, DC 

National Institutes of Health (NIH) 

GORMAN, Richard L., MD 

Associate Director for Clinical Research 

Division of Microbiology and Infectious Diseases/NIAID 

National Institute of Health 

Bethesda, MD 

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LIAISON REPRESENTATIVES 

American Academy of Family Physicians (AAFP) 

LOEHR, Jamie, MD, FAAFP 

Cayuga Family Medicine (Owner) 

Ithaca, NY 

American Academy of Pediatrics (AAP) 

BYINGTON, Carrie L., MD 

Chair, AAP Committee on Infectious Diseases 

H.A. and Edna Benning Presidential Professor of Pediatrics 

Associate Vice President for Faculty and Academic Affairs 

University of Utah Health Sciences Center 

Salt Lake City, UT 

American Academy of Pediatrics (AAP) 

KIMBERLIN, David, MD 

Red Book Editor 

Professor of Pediatrics 

Division of Pediatric Infectious Diseases 

The University of Alabama at Birmingham School of Medicine 

Birmingham, AL 

American Academy of Physician Assistants (AAPA)

LÉGER, Marie-Michèle, MPH, PA-C 

Senior Director, Clinical and Health Affairs 

American Academy of Physician Assistants 

Alexandria, VA 

American College Health Association (ACHA) 

EVEN, Susan, MD 

Executive Director 

Student Health Center 

University of Missouri 

Columbia, MO 

American College of Nurse Midwives (ACNM) 

HAYES, Carol E., CNM, MN, MPH 

Atlanta Perinatal Associates 

Atlanta, GA 

American College of Obstetricians and Gynecologists (ACOG) 

AULT, Kevin A., MD 

Professor and Division Director, General Obstetrics and Gynecology 

Department of Obstetrics and Gynecology 

Kansas City, KS 

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American College of Physicians (ACP) 

FRYHOFER, Sandra Adamson., MD, MACP 

Adjunct Associate Professor of Medicine 

Emory University School of Medicine 

Atlanta, GA 

American College of Physicians (ACP) (alternate) 

POLAND, Gregory A., MD 

Mary Lowell Professor of Medicine and Infectious Diseases 

Mayo Clinic 

Rochester, MN 

American Geriatrics Society (AGS) 

SCHMADER, Kenneth, MD 

Professor of Medicine-Geriatrics 

Geriatrics Division Chief 

Duke University and Durham VA Medical Centers 

Durham, NC 

America’s Health Insurance Plans (AHIP) 

NETOSKIE, Mark J., MD, MBA, FAAP 

Market Medical Executive, CIGNA 

Houston, TX 

American Medical Association (AMA) 

FRYHOFER, Sandra Adamson., MD, MACP 

Adjunct Associate Professor of Medicine 

Emory University School of Medicine 

Atlanta, GA 

American Nurses Association (ANA) 

RITTLE, Charles (Chad), DNP, MPH, RN, FAAOHN 

Assistant Professor, Nursing Faculty 

Chatham University, School of Health Sciences 

Pittsburgh, PA 

American Osteopathic Association (AOA) 

GROGG, Stanley E., DO, FACOP 

Associate Dean/Professor of Pediatrics 

Oklahoma State University-Center for Health Sciences 

Tulsa, OK 

American Pharmacists Association (APhA) 

FOSTER, Stephan L., PharMD, FAPhA 

Professor and Vice Chair, Department of Clinical Pharmacy 

University of Tennessee Health Sciences Center, College of Pharmacy 

Memphis, TN 

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Association of Immunization Managers (AIM) 

MOORE, Kelly, MD, MPH 

Medical Director, State Immunization Program 

Tennessee Department of Health 

Nashville, TN 

Association for Prevention Teaching and Research (APTR) 

McKINNEY, W. Paul, MD 

Professor and Associate Dean 

University of Louisville School of Public Health and Information Sciences 

Louisville, KY 

Association of State and Territorial Health Officials (ASTHO) 

DWELLE, Terry L, MD, MPHTM, FAAP, CPH 

State Health Officer 

North Dakota Department of Health 

Bismarck, ND 

Biotechnology Industry Organization (BIO) 

Day 1: Dr. Leonard Friedland (GSK) 

Day 2: Dr. Eddy Bresnitz (Merck) 

Council of State and Territorial Epidemiologists (CSTE) 

HAHN, Christine, MD 

State Epidemiologist 

Office of Epidemiology, Food Protection and Immunization 

Idaho Department of Health and Welfare 

Boise, ID 

Canadian National Advisory Committee on Immunization (NACI) 

GEMMILL, Ian MacDonald, MD, CCFP, FCFP, FRCP(C) 

Medical Officer of Health 

Kingston, Frontenac and Lennox & Addington Public Health 

Kingston, Ontario, Canada 

Infectious Diseases Society of America (IDSA) 

NEUZIL, Kathleen M., MD, MPH, FIDSA 

Vaccine Development Global Program (PATH) 

Clinical Professor 

Departments of Medicine and Global Health 

University of Washington School of Medicine 

Seattle, WA 

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Infectious Diseases Society of America (IDSA) (alternate) 

BAKER, Carol J., MD 

Professor of Pediatrics 

Molecular Virology and Microbiology 

Baylor College of Medicine 

Houston, TX 

National Association of County and City Health Officials (NACCHO) 

ZAHN, Matthew, MD 

Medical Director, Epidemiology 

Orange County Health Care Agency 

Santa Ana, CA 

National Association of Pediatric Nurse Practitioners (NAPNAP) 

STINCHFIELD, Patricia A., RN, MS, CPNP 

Director 

Infectious Disease/Immunology/Infection Control 

Children's Hospitals and Clinics of Minnesota 

St. Paul, MN 

National Foundation for Infectious Diseases (NFID) 

SCHAFFNER, William, MD 

Chairman, Department of Preventive Medicine 

Vanderbilt University School of Medicine 

Nashville, TN 

National Immunization Council and Child Health Program, Mexico

VILLASEÑOR RUIZ, Ignacio 

Directora del Programa de Atencion da la Salud de la Infancia y la Adolescencia / Director 

General, Child and Adolescent Health 

Centro Nacional Para la Salud de la Infancia Y La Adolescencia / National Center for Child and 

Adolescent Health 

Ministry of Health / Secretaría de Salud 

Mexico 

National Medical Association (NMA) 

WHITLEY-WILLIAMS, Patricia, MD 

Professor and Chair 

University of Medicine and Dentistry of New Jersey 

Robert Wood Johnson Medical School 

New Brunswick, NJ 

National Vaccine Advisory Committee (NVAC) 

ORENSTEIN, Walt, MD 

Chair, NVAC 

Associate Director, Emory Vaccine Center 

Emory University 

Atlanta, GA 

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Pediatric Infectious Diseases Society (PIDS) 

SAWYER, Mark H, MD 

Professor of Clinical Pediatrics 

University of California, San Diego School of Medicine 

San Diego, CA 

Pediatric Infectious Diseases Society (PIDS) (alternate) 

ENGLUND, Janet A., MD 

Professor, Department of Pediatrics 

Seattle Children's Hospital 

University of Washington 

Seattle, WA 

Pharmaceutical Research and Manufacturers of America (PhRMA) 

BRAGA, Damian A. 

President, Sanofi Pasteur 

Swiftwater, PA 

Society for Adolescent Health and Medicine (SAHM) 

MIDDLEMAN, Amy B., MD, MSEd, MPH 

Professor of Pediatrics 

Chief, Section of Adolescent Medicine 

University of Oklahoma Health Sciences Center 

Oklahoma City, OK 

Society for Healthcare Epidemiology of America (SHEA) 

WEBER, David, MD, MPH 

Professor of Medicine, Pediatrics, and Epidemiology 

University of North Carolina Schools of Medicine and Public Health 

Medical Director, Hospital Epidemiology and Occupational Health, UNC Health Care 

University of North Carolina 

Chapel Hill, NC 

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Meningococcal Submissions 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Student Health Services 

June 11, 2015 

Ms. Stephanie Thomas and the Advisory Committee on Immunization Practices, 

We feel that it is appropriate to give a cautious recommendation to the ACIP to 

recommend the immunization of adolescents and college age students against serogroup B 

meningococcal. As we know menigitieous causes significant morbidity and mortality worldwide 

and even more so in college age student due to their close proximity with each other, especially 

in living quarters. Utah department of health has also reported an increase in group B meningitis 

in Utah1

. 

However, we feel that caution must be taken and the roll out of this vaccine needs to be 

in a well-planned manner. The vaccines for Group B Meningitis is new, not even a year old in 

the US. We spoke with the Utah County immunization clinic and they do not carry the vaccine 

but it is available by special order. They estimate that it would cost $200 per dose and 2-3 doses 

are required. We am also cautious because the efficacy, and duration of protection is not yet 

fully understood. The expert state that they need a population-based study to be done and to do 

that study the vaccine would need to be widely used, such as after routine immunizations. 

Studies thus far also suggest that if the vaccine is widely used that it would produce herd 

immunity that would help protect those students who have not received the vaccine, due to cost 

or personal preference. Obviously cost would be a great concern to the cash strapped college 

student. We agree that this is an appropriate preventive measure that insurances should cover. 

The roll out of the vaccine needs to be done properly because for the general student population 

and the campus as a whole to benefit the majority of people need to be vaccinated, not once but 

receive 2-3 doses. The students will need to be well educated about the benefits and risks to the 

vaccine and how important it is that they return for a 2nd or 3rd dose. Limited studies have shown 

that people that only get one dose have a 7376% increase in bactericidal tiers against Group B 

Meningitis 6 months after the injection. While 99-100% those who receive 2-3 doses had 

increased bactericidal tiers against Group B Meningitis 6 months after the injection. Proper 

follow-up is going to be very important. 

We have partnered in the past with the Utah County Health Department to provide immunization 

on campus to students. We also have a presence at the county immunization coalition. The 

county is really best suited to undertake a mass vaccination effort for the student body. 

Especially since they are able to bill insurances and we are not. We would participate in this 

effort by helping to educating the student body, and facilitate a vaccine fair on campus. 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Overall, we feel that UVU is at low risk from an immediate Group B meningitis outbreak as we 

do not have traditional student dorms but have more apartment style 

800 West University Parkway MS200 Orem, UT 84058 Phone 801­

863-8876 • Fax 801-863-7056 

Student Health Services 

living for the student. Also UVU Student Health Services and UVU Student Wellness does a 

fantastic job in promoting prevention and healthy living. Preventing the danger of a future 

outbreak at UVU is important and that is why we agree with the recommendations to include this 

in routine immunization. To fully benefit from this insurance companies need to cover the 

vaccine and the roll out needs to be done in a well-planned out manner. 

Thank you for your consideration, 

Esme Anderson, APRN, FNP 

Director of Medical Services 

Nurse Practitioner 

Derrick Pickering, APRN, FNP 

Nurse Practitioner 

http://health.utah.gov/epi/diseases/meningococcal_disease/plan.pdf 

1.	 http://www.uptodate.com.xlib1.intermountain.net/contents/meningococcalvaccines?sou 

rce=search_result&search=serogroup+B+Meningococcal+Vaccine&selected Title=5~6#H28 

800 West University Parkway MS200 Orem, UT 84058 Phone 801­

863-8876 • Fax 801-863-7056 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Stephanie Thomas
 

Advisory Committee on Immunization Practices (ACIP)
 

1600 Clifton Road, N.E. 

Atlanta, GA 30333
 

ACIP@CDC.GOV
 

Dear Ms. Thomas: 

We, the University of Colorado Boulder Student Government, strive to promote a campus 

atmosphere that allows students to thrive & succeed. This includes a focus on protecting the 

health and well being of our students. Within the Student Government, we have made it a 

priority to keep our fellow students well informed about health risks, including from infectious 

diseases such as meningitis. We applaud both the University and our state government for 

making meningitis vaccines a priority for incoming students. Since we have become aware of 

the threat of meningitis B, we put forward the attached resolution to encourage ACIP to 

recommend that college students vaccine for college students as a positive step to maintaining 

our desired healthy student body. 

We feel strongly about this recommendation and attached a copy of the University of Colorado 

Boulder Student Government Resolution that was passed unanimously on June 4th, 2015. 

We hope that as you make your decisions on meningitis B that you keep our students, the 

students of the University of Colorado, and the students around our great nation in mind. 

Thank you for your service and commitment to keeping our nation healthy and for considering 

our resolution. 

Sincerely yours, 

Boneth Ahaneku 

President of Internal Affairs & 

Neuroscience and Molecular, Cellular, Developmental Biology Major at 

University of Colorado Boulder 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Sierra's Race Against Meningitis 

Stephanie Thomas
 

Advisory Committee on Immunization Practices (ACIP)
 

1600 Clifton Road, N.E. 

Atlanta, GA 30333
 

Dear Ms. Thomas & ACIP Members: 

We lost our daughter Sierra, April 10, 2007, to Meningococcal Meningitis, a vaccine preventable 

disease. Sierra was 2 months away from turning 21 years old, working her way through college to 

fulfill her dream of becoming an elementary school teacher. She was everything good in this 

world, never afraid to share her outlook on life with anyone and everyone. Easter morning 2007, 

Sierra was her happy, healthy, loveable self, by evening she become sick with classic flu-like 

symptoms that always disguise the killer bacteria working to destroy your body. Within 24 hours 

she was in the emergency room on a ventilator. The following morning, on our beautiful Sierra 

succumbed to the devastating bacteria that invaded her body, Meningococcal Meningitis. Our 

family was not aware of this fatal disease, or of the vaccine that could have prevented it, until it 

was to late. Our lives from that day forward would never be the same, we were now missing a 

huge piece of our life, a piece that could never be replaced, but her spirit lives on in us and guides 

us as we do everything we can to help others. 

Unfortunately we can’t change what happened to Sierra, or the many other victims of this 

devastating disease, but we can prevent this horrible tragedy from happening to anyone else. This 

is our goal. 

Sierra’s Race Against Meningitis came to be as our effort to get the word out about this horrible 

disease. 100% of our proceeds/donations go to free vaccination clinics and awareness of the 

disease. We have provided over 4300 free vaccinations in the last 8 years. We miss Sierra more 

then words can express, we find comfort in knowing we are doing our best to make sure others 

don’t have to go through what we have and continue to go through. 

We strongly believe that the meningitis B vaccine should be recommended the way the other 

meningitis vaccines are because we do not want to wait for an outbreak to occur and risk any 

lives. We respectfully ask ACIP members vote to recommend meningitis B vaccines be added 

the regular vaccination schedule. 

Thank you for considering our requests and for the work ACIP does to keep our nation healthy. 

Sincerely, 

Lisa & Jon Krizman 

Sierra’s Race Against Meningitis 

970-310-9103 

www.SierrasRaceAgainstMeningitis.com 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

June 2, 2015 

Ms. Stephanie Thomas 

Advisory Committee on Immunization Practices 

Centers for Disease Control and Prevention 1600 

Clifton Road, N.E. 

Atlanta, GA 30333 

Dear Ms. Thomas: 

I urge the Advisory Committee on Immunization Practices to consider recommending broader meningitis 

vaccination for youth and LGBT populations, especially those living with HIV. This issue rose to my 

level of consciousness as several recent unexplained outbreaks rocked California’s gay communities, one 

of which resulted in the death of a personal acquaintance. 

Similar meningitis B outbreaks on college campuses across California, including locally at UC Davis 

have been in the news. Those who are HIV positive seem to be at even greater risk for contracting the 

disease, accounting for more than half of the infections. 

The the danger to students living and socializing in close quarters and to younger members of the LGBT 

community, specifically those living with HIV, is both potentially grave and totally preventable. I 

understand that awareness campaigns and efforts to vaccinate are currently recommended at the hyper 

local level when there is an identified outbreak. Unfortunately, once an outbreak occurs it’s too late for 

those who are already infected and unknowingly putting their friends, neighbors, and sexual partners at 

risk. 

At the Sacramento LGBT Community Center we provide support to hundreds of LGBT youth ages 13-25 

every month, many of whom are homeless or experiencing other conditions that put them at higher risk 

for communicable and sexually transmitted diseases. Too often they do not know they are infected or 

wait too long to seek treatment because they lack health insurance and continue to spread infections. We 

work to educate them on their risks, provide HIV testing, and connect them with supportive health 

resources and insurance, but can only do so much with the tools available. While we may not yet have a 

vaccine to prevent the spread of HIV, the FDA has approved vaccines to prevent meningitis. I urge you 

to make them more available by recommending broader meningitis B vaccination for higher risk 

populations including young people living and socializing in close quarters as well as LGBT and HIV 

positive individuals before additional outbreaks occur and lives are lost. 

Sincerely, 

David Heitstuman 

Board President 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

ACIP 

Advisory Committee on Immunization Practices 

Office of Infectious Diseases 

Centers for Disease Control and Prevention 

Public Comment Sign-In Sheet 

(Please limit your comments to three minutes) 

June 2015 

Name: Steven Black, MD __________ 

Organization: Division of Infectious Diseases and Center for Global Health, Cincinnati 

Children’s Hospital Cincinnati, Ohio 

Mailing Address: 3333 Burnett Avenue 

City: _Cincinnati ___ State:__Ohio_____Zip: 45229 ______________ 

Phone Number: 510-219-7372 

E-mail Address: Stevblack@gmail.com 

ACIP Topic: Meningococcal Vaccination June 24, 2015 

Comments: I wish to present my perspective on the burden of meningococcal disease, the 

impact of disease on individuals who become ill and to support a universal adolescent 

recommendation for Meningococcal B vaccination. In my opinion, decision criteria for 

vaccination should be multifactorial and take other factors than cost-effectiveness into 

account. To not do so makes vaccination a cost management tool rather than a public health 

tool. Other factors that have been proposed include the morbidity and mortality of the 

disease, the potential to cause outbreaks, and impact on future productivity. Meningococcal 

disease has both a high case mortality and morbidity rate and outbreaks induce fear in the 

population. Furthermore, the disease has a great impact on families and friends of people 

who contract the disease. I wish to share one such story. After many decades of vaccine 

development, we now have the ability to control this disease. While it is relatively rare, it 

still causes more than 500 cases 50 deaths per year and leaves half of cases with life long 

disability. As care givers and physicians, we should seize the opportunity to address this 

disease burden. 

(Provide comment form to ACIP Staff) 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

June 1 9, 2015 

Dr. Jon athan Temte, Chair 

The Advisory Committee on Immunization Practices (ACIP) 

1600 Clifton Road, N.E., Mailstop A27 

Atlanta, GA 30333 

Email 

Re: NVIC Public Comment on ACIP Meningococcal Vaccine Sero Type B Recommendations 

Dear Dr. Temte, 

Attached is our public comment for the upcoming ACIP meeting on June 24 th. I would like to express 

my personal thanks for your efforts to make public comment available to those who list en to the 

meeting via webinar. While we are disappointe d that public comment will not be availa ble to those 

listening online, we are sincerely grateful for your offer to read our comment to the committee. It 

seems that most comment s given during ACIP meeting are about three to five minutes in length. The 

attached comment is abo ut 3 minutes in length. 

We are also appreciative that it would be a daunting task to make public comment available under the 

current format. It has been my experience that many who listen on the phone and in the room do not 

offer public comment. However, it is important t o creat e equity for the public to comment without 

having to journey to Atlanta . Perhaps it would be possible to split the public comment time equally 

between those online and those present and require registration on a first come first serve bas is with 

a time limit for individual comment s? 

For example, if the public comment session is 30 minutes, 15 minutes could be allotted to those 

online and those in the room with five people on the phone being able to give comment and five in the 

room giving comment , with each getting thre e minutes for comment . 

Again, we appreciate your efforts to make ACIP meetings more accessible to the public , as well as 

your service to the public as you step down from the committee. 

Please don’t hesitate to contact me with any concerns or questions regarding our comment at 

tkw.nvic@gmail.com . 

Best regards, 

Theresa Wrangham 

Executive Director 216 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Advisory Committee for Immunization Practices – June 24,

2015 National Vaccine Information Center Public Comment 

Thank you for the opportunity to provide public comment today. Founded in 1982, the nonprofit National Vaccine Information Center advocates for the institution of vaccine safety and 

informed consent protections in public health policies and laws. We support the availability of 

all preventive health care options, including vaccines, and the right of consumers to make 

educated, voluntary health care choices. 

Meningococcal disease is devastating to those stricken and the public has a right to utilize Men 

B vaccines. As the committee considers routinely recommending Men B vaccines, please 

consider the following information. 

The current U.S. population is estimated to be over 3211

 million, and according to the CDC, 

meningococcal disease in the U.S. ranges from 800-1,200 cases annually. A third of these cases 

are serogroup B,2

 with 60 percent of serogroup B cases occurring in children too young to 

benefit from Men B vaccines.3

 The CDC has also acknowledged that humans are the only 

natural reservoir for N. meningitides, and that as children grow to adulthood the vast majority 

will have bactericidal antibodies against this disease.4 

Additionally, a CDC report published in 2000 revealed that routine recommendation of 

meningococcal vaccines for college freshman living in dormitories was not cost-effective. The 

report stated it would take 300,000500,000 doses of vaccine annually to prevent 15-30 cases of 

disease and one to three deaths. The costs were $600,000 to $1.8 million to prevent one case of 

disease, and $7 million to $20 million to prevent one death.5

 Although this report is precedes 

licensure of Men B vaccines, Men B vaccine cost-effectiveness findings would be similar. 

Because ACIP’s routine recommendations often translate into legal vaccine mandates in many 

states,5

 choice and recommendations versus vaccine requirements were unifying themes noted in 

the CDC’s 2011 stakeholder report on meningococcal vaccines.6 

We have listened with deep sympathy to experiences shared by parents, whose children and 

families been devastated by invasive meningococcal disease. During ACIP meetings and the 

CDC’s 2011 public engagement on meningococcal vaccines, some parents said their health care 

1 U.S. Census Bureau. U.S. & World Population Clock. 2 CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases The Pink Book: Course 

Textbook.13th Edition (2015). CDC updated Jun. 17, 2015. 

3 Ibid 

4 CDC. Manual for Surveillance of VPD: Chapter 8: Meningococcal Disease. CDC updated 

Apr. 1, 2014. 5 CDC. Meningococcal Disease and College Students: Recommendations of 

the Advisory Committee on Immunization Practices (ACIP). MMWR - 49(RR07;11-20). 

Jun. 30, 2000. 

5 National Conference of State Legislatures (NCSL). Meningitis Laws at a Glance. NCSL 

updated 2012. 

6 CDC. Engagement Project Report: Meningococcal Vaccines and Infants/Toddlers. Executive 

Summary. Summer 2011. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

providers did not make them aware of meningococcal vaccine availability. These parents had a 

right to know about the benefits and risks, and availability of meningococcal vaccines so they 

could make an informed decision for their children. 

However, with regard to ACIP recommending that all children get Men B vaccines, the data is 

clear that a universal use recommendation is not justified. It would have far reaching 

consequences that will be costly and unnecessarily burdensome to parents, adults and 

government agencies. 

NVIC respectfully requests the ACIP to vote against a Men B vaccine universal use 

recommendation. We encourage the ACIP and CDC to revisit the stakeholder report and the 

need for greater flexibility in ACIP recommendations. 

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1930 Ninth Avenue, Helena MT59601 

Phone: 406- - 457 8900 

Fax:406- - 447 8443 

publichealth@lccountymt.gov 

www.LewisAndClarkHealth.org 

Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

June 19, 2015
 

Stephanie Thomas
 

Advisory Committee on Immunization Practices
 

1600 Clifton Road N.E.
 

Atlanta, Georgia
 

30333
 

Dear Ms. Thomas:
 

I am writing on behalf of Lewis & Clark Public Health in Montana to encourage the Advisory
 

Committee on Immunization Practices to broaden the meningococcal recommendation to include
 

serogroup B immunization for adolescent students and college students.
 

Preventing the spread of meningitis is a priority of our community and raising awareness of the
 

need to be vaccinated is a particular focus of our Health Department. Many young adults and
 

their families have been impacted by this terrible disease. This will continue to happen unless
 

more students have access to vaccinations.
 

It’s important to point out that the FDA has expedited the approval of vaccines against
 

meningococcal serogroup B because they acknowledge the growing concern and the importance
 

of preventing outbreaks of the disease. However, in order for people to have access, it’s critical
 

that ACIP expands the recommendation.
 

Based on this, we urge your timely review and approval of a broad, recommendation for routine
 

immunization against meningitis B so we are able to keep our youth and young adults safe and
 

avoid another tragic outbreak.
 

Thank you for your consideration of this important request.
 

Sincerely,
 

Melanie Reynolds, M.P.H.
 

Health Officer, Lewis and Clark Public Health
 

Our mission is to improve and protect the health of all Lewis and Clark County residents. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Stephanie Thomas 

Advisory Committee on Immunization 

Practices 1600 Clifton Road, N.E. 

Atlanta, GA 30333 

Dear Ms. Thomas 

The Osteopathic Physicians and Surgeons of Oregon (OPSO) represents over 1,300 physicians, 

residents, and medical students in Oregon. As part of our mission is to ensure the highest quality 

health care to the people of Oregon, OPSO strongly supports increasing immunization rates 

among Oregonians. Vaccinations against diseases such as bacterial meningitis are one of the 

most significant public health achievements of our time. 

To achieve increased immunizations, OPSO encourages the Advisory Committee on 

Immunization Practices to consider adopting recommendations requiring meningococcal 

serogroup B immunization for adolescent and college students. As you know, a number of 

college campuses have recently experience outbreaks of serogroup B meningococcal disease. A 

recommendation from ACIP requiring immunization would be a significant step in preventing 

the death and disability brought on by an outbreak. 

We hope you will address this issue at your upcoming meeting. I and the OPSO Board of 

directors would be happy to discuss with you in greater detail if you have any questions. 

Thank you for your kind consideration. 

Sincerely, 

David Walls 

Executive Director 

4380 SW Macadam Ave., Suite 185 | Portland OR 97239 | p: 503.299.6776 f: 503.241.4856 

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Advisory Committee on Immunization Practices (ACIP)	 Summary Report June 24-25, 2015 

Thomas, Stephanie B. (CDC/OID/NCIRD) 

From: Peter E. Johnsen, M.D. <johnsenp@Princeton.EDU>
 

Sent: Friday, June 19, 2015 3:39 PM
 

To: Advisory Committee on Immunization Practices (CDC)
 

Cc: Charlotte Treby M. Williams; Karen A. Jezierny; John Kolligian Jr.
 

Subject: MenB vaccine recommendations
 

Dear Members of the ACIP subcommittee on meningitis,
 

As you are aware, Princeton University experienced an outbreak of meningococcal B disease in
 

2013-14. There were 9 cases related to a unique outbreak strain. The CDC indicated that our
 

attack rate was greater than 130/100,000. There was 1 death associated with this outbreak; 1
 

survivor is reported to have had hearing impairment, 1 survivor continues to have chronic daily
 

headaches, and 1 survivor had cognitive impairment (which appears to have resolved after a
 

number of months). Even one death is tragic; since we had several students in multi-system
 

failure, we consider ourselves fortunate that the case-fatality rate was not even higher, and that
 

we did not experience more residual effects.
 

As you know, our outbreak was not temporally clustered, but was sustained over a period of
 

approximately one year. Of the 7 Princeton students involved, only one presented with
 

symptoms considered typical of meningococcal disease.
 

Other presentations:
 

•		 One presented with a sore throat, was placed on penicillin. He was aware of our 

meningitis outbreak and asked to be reevaluated 12 hours later because he was concerned 

his situation was becoming worse. 

•		 One presented with report of a fever the night before but looked well on presentation in 

the morning and had only a low grade fever. Because of our awareness of meningococcal 

disease on campus we observed her in the Infirmary; when her white blood count 

returned elevated we sent her to the Emergency Department at a nearby hospital. A short 

time later she developed a typical rash. 

•		 Another student presented with fever, exudative tonsillitis, and a positive rapid strep test. 

We observed him in the Infirmary and, in the middle of the night, he developed the 

classical purpuric rash. 

•		 This is not an easy disease to detect early in a student population. Our experience has 

been that our students appeared to compensate fairly well over the first 12-18 hours, and 

then had a sudden precipitous drop. Establishing an alternative diagnosis, such as 

streptococcal tonsillitis or influenza, does not exclude meningococcal disease. Most 

colleges and universities do not have the ability to monitor patients overnight. The vast 

majority of meningococcal cases are sporadic, which means that clinicians will not have 

the high index of suspicion that we developed during our outbreak. 

Despite an aggressive hygiene campaign, we continued to see cases every few weeks in the Fall 

of 2014. We initiated a vaccine campaign in December 2014 under an Investigational New Drug 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

protocol. We ultimately achieved approximately 98% first dose (and 94% second dose) coverage 

of our undergraduate body. We had no subsequent cases among our students. There was one 

additional case involving a student at another university who had had contact with Princeton 

students, suggesting asymptomatic nasopharyngeal carriage persisted and herd immunity was not 

established. 

Vaccine cost will factor in to any decision process. The cost to a university of a case of 

meningococcal disease can be enormous. While there are costs in terms of human suffering and 

direct medical / vaccine costs, there is also the cost associated with developing an infrastructure 

on the fly to cope with a possible outbreak. There is a cost in the enormous number of personhours invested in dealing with an outbreak and the level of public anxiety. There are opportunity 

costs associated with diversion of medical and other resources. Costs cannot simply be measured 

in terms of quality life years saved. 

1

It seems anomalous that, in New Jersey, incoming residential college students are required by law 

to have documentation of meningococcal ACYW vaccine, and are not allowed to register for 

classes if they cannot provide documentation, but for meningococcal B disease, which constitutes 

as significant a threat, there is no recommendation. 

I have informally reviewed much of what I’ve written here with several member of the 

subcommittee in the past. I recognize that there are remaining technical questions about the 

vaccine in terms of breadth of coverage against different strains, effect on nasopharyngeal 

carriage, and duration of protection. These questions obviously must be addressed. I also 

recognize that cost is a major factor that must be considered. However, given that meningococcal 

disease is difficult to diagnose on a campus in the stage at which it is most curable, and that 

current recommendations do not address preventing the majority of cases (primarily sporadic), I 

do not see alternatives to vaccination if we are to prevent the tragic outcomes of this disease. I 

would urge that you support a strategy that would allow insurance coverage of this vaccine, as for 

other preventive vaccines. 

Peter Johnsen, MD 

Director of Medical Services 

Princeton University 

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The Federation of Independent Illinois Colleges and Universities 

Adler School of 

Professional Psychology 

Augustana College 

Aurora University 

Benedictine University 

Blackburn College Bradley University 

Chicago School of 

Professional Psychology 

Columbia College Chicago 

Concordia University 

DePaul University 

Dominican University 

East-West University 

Elmhurst College 

Eureka College 

Greenville College 

Illinois College 

Illinois College of Optometry 

Illinois Institute of Technology 

Illinois Wesleyan University 

Judson University 

Knox College 

Lake Forest College 

Lakeview College of Nursing 

Lewis University 

Lincoln College 

Loyola University of Chicago 

MacCormac College 

MacMurray College 

McKendree University 

Midwestern University 

Millikin University 

Monmouth College 

National University of 

Health Sciences 

National-Louis University 

North Central College 

North Park University 

Northwestern University 

Olivet Nazarene University 

Principia College 

Quincy University 

Resurrection University 

Robert Morris University 

Rockford University 

Roosevelt University 

Rosalind Franklin University 

Of Medicine and Science Rush University 

Saint Anthony College of Nursing 

Saint Augustine College 

Saint John's College 

Saint Xavier University 

School of the Art Institute 

Shimer College 

Trinity Christian College 

Trinity College of Nursing 

Trinity International University 

University of Chicago 

University of St. Francis 

VanderCook College of Music 

Wheaton College 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

June 22, 2015 

Larry K. Pickering M.D.
 

Executive Secretary
 

Advisory Committee on Immunization Practices
 

1600 Clifton Road, N.E., Mailstop A27
 

Atlanta, GA 30333 

Via: Email PDF
 

Dear Dr. Pickering,
 

As the president of the Federation of Independent Illinois Colleges and 

Universities, I respectfully write to urge the Advisory Committee on Immunization
 

practices (ACIP) to endorse at its June 2015 meeting routine recommendations for the
 

immunization of adolescents and college-age students against serogroup B meningococcal
 

disease.
 

As an advocacy organization that represents over 200,000 students, as well as over 60,000 

employees, we are understandably concerned about meningitis B given the high risk age
 

cohort and environment (dorms and apartments) unique to our students. The availability of
 

these vaccines for students as soon as possible will help to minimize the possibility of
 

future tragedies similar to the outbreaks experienced by a number of college campuses
 

across the country. 

The Federation of Independent Illinois Colleges and Universities is the oldest private
 

college association in the nation. The Federation is an advocacy organization that represents
 

the public policy interests of Illinois’ non-profit colleges and universities. With a
 

membership of sixty institutions from all regions of the state, the Federation is the unified
 

voice on behalf of the independent not for profit sector of higher education in Illinois. 

Thank you for your consideration, and the work that you do to secure the health of our
 

citizens.
 

Regards, 

David W. Tretter
 

President
 

123 South Second Street. Springfield, Illinois 62704 • 217.789.1400 • FAX 217.789.6259 

Healthier Colorado 

1536 Wynkoop St., Suite 109 

Denver, CO 80202 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Dr. Tom Frieden 

Director, Centers for Disease Control & Prevention 1600 

Clifton Rd. 

Atlanta, GA 30329 

Dear Dr, Frieden, 

Healthier Colorado is a nonpartisan, nonprofit organization dedicated to ensuring that the voices 

of all Coloradans are heard by our public officials on issues concerning health. We believe every 

Coloradan should have access to the basic elements of healthy living. We believe immunizations 

are a vital tool to keep our communities safe and healthy, and the federal list of recommended 

vaccines has a major impact on who has access to these vaccines. 

We, the undersigned, urge the federal Advisory Committee on Immunization Practices to 

formally include the meningitis B vaccine on the list of recommended vaccines for Americans. 

This is a common-sense suggestion that will reduce the risk of outbreaks on college campuses 

and save lives. 

One fifth of all meningococcal infections occur in young adults between the ages of 14 and 24, 

and college students are at particularly high risk because dormitories are ideal environments for 

spreading this disease. Over the past months, we have seen the danger of not vaccinating. Six 

students and one parent of a student from the University of Oregon contracted the disease this 

year, resulting in the death of one student athlete in February. Other colleges and universities 

such as Princeton, Yale, Providence College, Oregon State and UC Davis have also experienced 

outbreaks of meningitis B. And these outbreaks are very serious. According to the CDC, the 

fatality rate of this disease is between 10 and 15 percent. Even with recovery, 19 percent of those 

affected suffer from complications, including severe damage to the nervous system, deafness, 

brain damage and loss of limbs. 

The FDA licensed the meningitis B vaccine in October 2014, and doctors agree that it is 

perfectly safe. Other countries, including Canada, Australia, and several European nations 

recommend meningitis B vaccinations for all young adults. By making this simple change to the 

ACIP list of recommended vaccines, we can save lives and reduce medical costs. We urge the 

ACIP to make this change. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Greg Abernathy 

71 Wheat Way 

Fairplay, CO 80440 

Heidi Anderson 

8878 Partridge St 

Littleton, CO 80126 

Anita Anthony-Huebert 

1011 Amsterdam Dr 

Colorado Springs, CO 80907 

Diana Avery 

1210 Harrison Rd 

Colorado Springs, CO 80905 

Dana Barela 

601 Somerset Dr 

Golden, CO 80401 

Joie Blue Jay 

950 S Washington St 

Denver, CO 80209 

Patty Boyd 

11625 W 28th Pl 

Lakewood, CO 80215 

Jackie Brown 

9 Summit Rd 

Lamar, CO 81052 

Rakesh Chandranatha 

16259 W 10th Ave J5 

Golden, CO 80401 

Julie Alt 

PO Box 2006 

Eagle, CO 81631 

James Andrus 

417 S Cedar Street Apt 30 

Cortez, CO 81321 

Bob Armintor 

1404 N Prospect St 

Colorado Springs, CO 80907 

Chloe Bailey
 

600 Grant St Suite 300 

Denver, CO 80206 

Kay and John Bengston 

23873 E Phillips Pl
 

Aurora, CO 80016 

Mary Boland 

288 Cabin Dr
 

Carbondale, CO 81623 

Shari Bradley
 

7550 Eaton St
 

Arvada, CO 80003 

Leslie Browning 

415 Mountain Village Blvd 

Unit 9103 

Mountain Village, CO 81435 

Linda Chase 

1640 Bellaire 

Denver, CO 80220 

Dina Anderson 

277 S Coolidge St 

Aurora, CO 80018 

Lori Anne Reinwald 

12510 W 85th Cir 

Arvada, CO 80005 

Linda Auld 

1917 Wallenberg Dr 

Fort Collins, CO 80526 

Patricia Baker 

1040 Kearney St 

Denver, CO 80220 

Catherine Blackford 

2121 E 16th Ave 

Denver, CO 80206 

Bernadine Bonfadini 

21290 El Rocio Vw 

Fountain, CO 80817 

Don Brenneman 

5955 Vista Ridge Pt Apt 101 

Colorado Springs, CO 80918 

Samuel C. Riccillo 

3275 Abby Ln 

Pueblo, CO 81004 

James A Clark Jr 

510 Quebec Pl 

Colorado Springs, CO 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

80911 

Jane Clevenger
 

5337 Fox Holw
 

Loveland, CO 80537 

Norvelle Couch 

10411 Drake Pl
 

Parker, CO 80134 

Michael Criswell 

4230 Hollow Rd 

Colorado Springs, CO 80917 

Susan Donaldson 

1417 Rembrandt Rd 

Boulder, CO 80302 

Geraldine Duffy
 

306 Hilltop Dr
 

Bayfield, CO 81122 

Hillary Elliott 

2925 N Elizabeth St
 

Denver, CO 80205 

Edgardo Fernandez
 

49 S Eagle Crk 

Aurora, CO 80012 

Marlene Cohen
 

1462 Raindrop Way
 

Castle Rock, CO 80109 

Ann Craig, MD
 

3830 Roxbury Ct
 

Colorado Springs, CO 80906 

Spencer Dean
 

5089 W 73rd Ave
 

Westminster, CO 80030 

Mark Dorr 

801 E Drake Rd Apt 72 

Fort Collins, CO 80525 

Lynda Dulany 

PO Box 33 

Orchard, CO 80649 

Kim Erickson 

789 Sherman St Unit 3101 

Denver, CO 80203 

Susie Fishman 

288 Edwards Village Blvd 11C
 

Edwards, CO 81632 

Ken Connell
 

2511 E 104th Ave Unit 267 

Thornton, CO 80233 

Terry Creech Brunt
 

14473 S Elk Creek Rd 

Pine, CO 80470 

Marcy Donaldson 

1111 Ash St Apt 306 

Denver, CO 80220 

Linda Drescher
 

9 S Holman Way
 

Golden, CO 80401 

Carlene Dumont
 

9218 W Wesley Dr
 

Lakewood, CO 80227 

Megan Faber
 

1285 S Sherman St
 

Denver, CO 80210 

Alexandra Fogarty 

2752 E Caley Ave
 

Centennial, CO 80121 

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Christine Foote 

7601 Rd 41 

Mancos, CO 81328 

Sara Fox 

2036 Mesa Dr 

Boulder, CO 80304 

Sara Froelich 

831 Uinta Way 

Denver, CO 80230 

Lindsay Gartner 

201 North Rd 

Durango, CO 81303 

Scott Gerardy 

3335 Atwood Dr 

Loveland, CO 80538

Lynne Glaeske 

3945 S Uinta St 

Denver, CO 80237 

Shirley Goff 

1714 Naples Ln 

Longmont, CO 80503 

Linda Graae 

309 E Swallow Rd 

Fort Collins, CO 80525 

Alice Green 

PO Box 723 

Wheat Ridge, CO 80034 

Felicia Griffin 

11233 E Harvard Dr 

Aurora, CO 80014 

Jeri Groves 

28867 Cedar Cir 

Evergreen, CO 80439 

Alan Hansen 

1058 S Dahlia St A20 

Glendale, CO 80246 

Anne Harrison 

1041 Boxelder Cir 

Longmont, CO 80503 

Sarah Haworth 

840 Bluegrass Way 

Windsor, CO 80550 

Anne and John Hedberg 

7 Heather Way 

Golden 80401 

Janet Heller 

16697 E Hialeah Ave 

Centennial, CO 80015 

Kathleen Herrera 

PO Box 140924 

Edgewater, CO 80214

Lauren Howe 

1057 Emerson St 

Rochester, NY 14606 

Steven J Cozzi 

10340 W 44th Ave #2A 

Wheat Ridge, CO 80033 

Rebecca J Goveia 

854 W Battlement Pkwy 

Parachute, CO 81635 

Victoria Francies 

1102 W 13th Ave 

Denver, CO 80204 

Dianna Genovese 

1670 E Cheyenne Mt Blvd 

Colorado Springs, CO 

80906 

Tom Goddard 

35520 County Road 22 

Holyoke, CO 80734 

Jane Graham 

909 Centre Ave #321 

Fort Collins, CO 80526 

Julie Griffith 

3570 Cloverleaf Dr 

Boulder, CO 80304 

Ronald Harden 

3125 Elevado Ct 

Loveland, CO 80538 

Stuart Heasman 

705 Hunter Drive Apt. 

1407 

Pueblo, CO 81001 

Peggy Herbertson 

33442 County Rd 25 

Elizabeth, CO 80107 

Erik Hvoslef 

PO Box 688 

Salida, CO 81201 

Tom Jackson 

1535 Franklin St Apt 9B 

Denver, CO 80218 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Elizabeth Jane LeCates 

13606 E Bates Ave Apt 203 

Aurora, CO 80014 

Rose Jones 

1226 Silverqueen Rd 

Pueblo, CO 81008 

Chris Kermiet 

2267 Hudson St 

Denver, CO 80207 

Tricia Kob 

1918 Leicester Way 

Fort Collins, CO 80526 

Abigail Lang 

227 Marie St 

Ridgway, CO 81432 

Robert Levitt 

512 Duke Ln 

Fort Collins, CO 80525 

Stephanie Longo 

613 W Bowman Ave 

Woodland Park, CO 80863 

Bruce M. Cratty 

2525 S Humboldt St 

Denver, CO 80210 

Tara Manthey 

2870 Leyden St 

Denver, CO 80207 

JoLynn Jarboe 

3204 S Dahlia St 

Denver, CO 80222 

Vickry Kayser 

411 N Cedar St 

Colorado Springs, CO 80903 

Richard Kite 

Brown Street 

New York, NY 12345 

Jan Kochmeister 

12587 W Dakota Ave Apt 111 

Lakewood, CO 80228 

LisaJo Laptad 

1613 Carmel Dr 

Colorado Springs, CO 80910 

Bill Lindsay 

3755 Tennyson St 

Denver, CO 80212 

Cynthia Dawn Loreth 

12438 E Amherst Cir 

Aurora, CO 80014 

Mary M. O'Leary 

12334 31st Ave NE #401 

Seattle, WA 98125 

Liza Marron 

PO Box 301 

Saguache, CO 81149 

Margaret Johnson 

PO Box 18979 

Golden, CO 80402 

Chris Kermiet 

2267 Hudson St 

Denver, CO 80207 

Michelle Kneipper 

12297 E Iowa Dr 

Aurora, CO 80012 

Maya Kurtz 

336 Park Dr 

Glenwood Springs, CO 81601 

Margaret Latourrette 

624 S Oneida Way 

Denver, CO 802324 

Becky Lindsay 

3755 Tennyson St 

80212 

Judy Lubow 

106 Granada Ct 

Longmont, CO 80504 

Marcia Maccaux 

505 E Simpson St Apt B 

Lafayette, CO 80027 

Marty Martinez 

6400 Porter Way 

Commerce City, CO 80022 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Shelly McCumber
 

2302 Ash Ave
 

Greeley, CO 80631 

Amanda McNeill Cortez,
 

CO 81321 

F Meek
 

PO Box 773510 

Steamboat Springs, CO 80477 

Mirna Miranda 

3409 N Overland Trl
 

LaPorte, CO 80535 

Chris Moore
 

2126 S Josephine St
 

Denver 80210
 

Martha Obermiller
 

907 Santa Fe Dr
 

Denver, CO 80204 

Richard P. Handler, M.D. 

32865 Saint Moritz Dr
 

Evergreen, CO 80439 

Robert Powell
 

6992 Blackhawk Pl
 

Colorado Springs, CO 80919 

Celia Roberts
 

PO Box 5 

Paonia, CO 81428 

Richard McKee 

1037 Champion Cir
 

Longmont, CO 80503 

Donna McWhirter
 

2539 Patriot Hts
 

Colorado Springs, CO 80904 

Rebecca Meylor
 

2627 S Osceola St
 

Denver, CO 80219 

Paul Moe 

13123 E 16 Ave
 

Aurora, CO 80045 

Tony Namaste' Tucker
 

313 E Iowa Ave
 

Berthoud, CO 80513 

Keith Ohler
 

1950 Trenton St Apt 441 

Denver, CO 80220 

Louis Palazzini 

930 Tucson St
 

Aurora, CO 80011 

Jeanne Puerta 

7505 W Yale Unit 1703 

Denver, CO 80227 

Kathryn Rose
 

2749 Lafayette St
 

Denver, CO 80205 

Lyric McKnight
 

2971 S Utica St
 

Denver, CO 80236 

Jackie Meehan
 

157 Cherry Cir
 

Fountain, CO 80817 

Thomas Michaels
 

5304 Elm St
 

Lakewood, CO 80228 

Sarah Moore 

207 S Jefferson 

Loveland, CO 80537 

Molly North 

4401 Vallejo St
 

80211
 

Erik Ortiz
 

1240 Jasmine St
 

Denver, CO 80220 

Cheryl Passion 

3320 Dover Dr
 

Boulder, CO 80305 

Eric Reger
 

1432 E Long Pl
 

Centennial, CO 80122 

Bernardo Sanchez V.
 

2203 Marshfield Ln 

Fort Collins, CO 80524 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Rachel Scarlata 

3855 Elk Rdg N 

Divide, CO 80814 

Catherine Sees 

2570 S Dayton Way Apt G 

Denver, CO 80231 

Tiffany Snyder 

175 S 35th St 

Boulder, CO 80305 

Jen Stanton 

4245 County View Way 

Castle Rock, CO 80104 

Dan Stinchcomb 

8409 S County Rd 3 

Fort Collins, CO 80528 

Bruce Stotts 

2207 Creststone Ct 

Fort Collins, CO 80525 

Kathleen Sweeney 

3544 Van Teylingen Dr Apt B 

Colorado Springs, CO 80917 

Norman Traum 

1478 N Franklin Ct 

Louisville, CO 80027 

Rachel Schmela 

6053 S Paris St 

Greenwood Village, CO 80111 

Ken Singer 

850 Apple Valley Rd 

Lyons, CO 80540 

Steven St. Clair 

2305 Bronquist Rd 

Pueblo, CO 81005 

Marc Stein 

19928 Chisholm Trl 

Monument, CO 80132 

Carol Stirling 

5888 Kingsfield St 

Castle Rock, CO 80104 

Jennifer Swan 

630 E St 

Salida, CO 81201 

Cathy Taubman 

2475 S Madison St 

Denver, CO 80210 

Jackie Tulli 

3604 E Uintah St Apt 29 

Colorado Springs, CO 80909 

Ronald Schwegel 

444 Nova Rd 

Pine, CO 80470 

Mary Smith 

29932 J Rd 

Hotchkiss, CO 81419 

Barbara Stanford Tanguma 

8222 Ammons Cir 

Arvada, CO 80005 

Mark Steinke 

2441 Julian St 

80211 

Jim Stone 

6371 W Fremont Dr 

Littleton, CO 80128 

Cyndy Swanson 

865 Sun Valley Dr 

Woodland Park, CO 

80863 

Linda Tibbets 

PO Box 1223 

Dolores, CO 81323 

James Vallejos 

2044 Havana St 

Aurora, CO 80010 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Chad Van Dam 

652 E 7th Ave 

Durango, CO 81301 

Patrick Watson 

921 Detroit St 

Denver, CO 80206 

Erika Wey 

11953 Clay Ct 

Westminster, CO 80234 

R William Schier 

2535 Race St 

Denver 80205 

Martha W D Bushnell 

502 Ord Dr 

Boulder, CO 80303 

Susan Welty RN 

372 Silver Circle Dr 

Westcliffe, CO 81252 

Venis White 

4460 W 111th Ave 

Westminster, CO 80031 

Jacob Williams 

2024 Clipper Dr 

Lafayette, CO 80026 

Marlene Waite 

6979 S. Elk Ct 

Aurora, CO 80016 

Craig Wesson 

10355 Dover St Apt 

1416 

Westminster, CO 

80021 

Cody Wieben 

22089 R Rd 

Cedaredge, CO 81413 

Jeanette Williams 

3610 Race St 

80205 

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Isabelle Williams 

648 Laredo St 

Aurora, CO 80011 

Colette Winslow 

6931 Wolff St 

Westminster, CO 80030 

Martin Wong 

2400 iris 

Boulder, CO 80304 

Maydean Worley 

1232 24th Avenue Ct 

# G4-1 Greeley, CO 80634 

80233 

Walter Young 

 14945 Foothill Rd 

 Golden, CO 80401 

Ruth Zimmerman 

 2501 E104 Ave 

 Denver, CO 

 

 

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June 24, 2015 

 

 

 

 

–

 

Confederation of Me ningitis Organisations Committed to preventing meningitis worldwide, because we can and we should. 

Administrative Address: 

100Roberts Road, Subiaco, Western Australia 6008 

PO Box 855, West Perth, Western Australia 6872 

Phone +61 8 9489 7791 

comomeningitis@ichr.uwa.edu.au www.comomeningitis.org 

Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

To the members of the Advisory Committee on Immunization Practices (ACIP): 

Thank you for your hard work and dedication to making our world better by advancing sound 

immunization practices to protect your citizens against preventable illness and death. The 

Confederation of Meningitis Organisations (CoMO) joins with you in that goal, and is dedicated 

to preventing meningitis globally by ensuring families worldwide have access to early diagnosis, 

preventative measures, and quick treatment. 

Approximately one-third of meningococcal disease cases in adolescents in the US are caused by 

serogroup B. Adolescents and young adults have the highest incidence of carriage in all age 

groups and are most vulnerable. They also interact with siblings and put younger children and 

babies at risk in the roles of helpers and babysitters. Please use your knowledge, the evidence, 

and your power to help us prevent meningitis from affecting others by recommending a routine 

vaccination against serogroup B meningococcal disease, making true and broad protection for 

teens a reality. We need you to take this step to fully cover the majority of people who want to 

protect themselves and their children from meningitis which, as you know, can kill or disable in 

hours. 

 

In essence, our goal is to prevent meningitis worldwide because we can and we should. As 

individual members of CoMO, we unfortunately know first-hand the devastating effects of 

meningitis. Imagine losing your child or watching them become disabled for life to a 

vaccinepreventable disease, knowing that a vaccine was available. Although meningitis cases are 

relatively rare when compared to other diseases, the effects have been devastating to many. No 

one can put a price on the life of a human being, especially a child with the potential for a bright 

future. 

We applaud the action taken by health authorities in the UK and Canada to protect the vitality 

and possibility of teenagers and young adults in their nations. Surely if there is help at hand, you 

would take this step? CoMO strongly urges you and your ACIP colleagues to follow the path 

created by the U.S. Food and Drug Administration in recommending the meningococcal B 

vaccine. Our children and young people deserve a full and fighting chance to live long and 

healthy lives. 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Together, we must Join Hands Against Meningitis. We – the 43 member organisations of
 

CoMO and in particular the 8 US-based organisations – are counting on you. 

Thank you,
 

The Confederation of Meningitis Organisations
 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Thomas, Stephanie B. (CDC/OID/NCIRD)
 

From: Kimberly Coffey Foundation 

<kimberlycoffeyfoundation@gmail.com> 

Sent: Tuesday, June 23, 2015 2:57 PM 

To: Advisory Committee on Immunization Practices (CDC) 

Subject: HIGH PRIORITY MENINGOCOCCAL SEROGROUP B VACCINE 

RECOMMENDATION 

Dear Dr. Jonathan L. Temte and Dr. Cindy Weinbaum: 

Below is my testimony from the Feb 2015 meeting: 

Three years ago today, my 17-year-old daughter Kimberly Coffey from New York, should have 

graduated with her senior high school class. Instead she was buried 3 days earlier as she died 

from serogroup B meningococcal disease. I had the false sense of security that Kim was 

completely protected against this horrific disease when she was vaccinated with Menactra. 

Unfortunately, I found this not to be true as I watched my healthy daughter die a terrible death 

from meningococcemia over the course of 9 days and ultimately be declared brain dead. 

Serogroup B vaccination would have saved my daughter's life if it had been available. 

Please make these vaccines available to all instead of only to limiting to college outbreaks and 

patients with complement deficiencies. 

https://youtu.be/WFcQzl4qFFQ 

Sincerely, 

Patti Wukovits, R.N. 

Executive Director 

Kimberly Coffey Foundation 

PO Box 344 

Massapequa Park, NY 11762 

www.kimberlycoffeyfoundation.org 

(516) 982-1433 

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Advisory Committee on Immunization Practices (ACIP) Summary Report June 24-25, 2015 

Ms. Stephanie Thomas June 23, 2015 

Advisory Committee on Immunization
 

Practices Centers for Disease Control and
 

Prevention 1600 Clifton Road, N.E. 

Atlanta, GA 30333 

Dear Ms. Thomas:
 

On behalf of the membership of The Wall Las Memorias Project, I strongly urge the Advisory
 

Committee on Immunization Practices to consider recommending broader meningitis vaccination
 

for youth and LGBT populations, especially those living with HIV.
 

There is no doubt that those who are at risk for HIV are more likely to contract meningitis B. 

From various reports, young people living in close proximity, such as college, university dorms
 

are also at risk. The most vulnerable are those from underserved, homeless and immigrant
 

populations. Due to economic status many of our people have to love in close living quarters
 

and this is often a breeding ground for meningitis. 

The Wall Las Memorias Project has provided HIV prevention and testing services to the Latino 

and LGBTQ community and have fought for better health care coverage for our people.
 

Today, the Advisory Committee can contribute greatly to improving the quality of life for
 

millions of Californians.
 

Thank you, 

Richard Zaldivar 

Executive Director 

5619 Monte Vista St., Los Angeles, CA 90042 * P-323-257-1056 * F-323-257-1095 * www.thewalllasmemorias.org 

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June 22, 2015 

Stephanie Thomas 

Advisory Committee on Immunization Practices (ACIP) 

1600 Clifton Road, NE 

Atlanta, GA 30333 

Re: Recommendation for meningitis B immunization 

Dear Ms. Thomas: 

We are members of the Health Policy Council, which is a network of physicians who also serve 

as legislators in statehouses across the country. The Health Policy Council is sponsored by the 

Alliance for Patient Access*. As legislators, we have a vested interest in the safety of higher 

education in our respective states. As physicians, we recognize the importance of vaccination 

against preventable disease and protection for public health. 

Therefore, in our capacity as both lawmakers and health care providers, we urge the Centers for 

Disease Control and Prevention to adopt a comprehensive recommendation for immunization 

against serogroup B meningococcal disease. 

Meningitis B accounts for the majority of bacterial meningitis cases in adolescents, according to 

the National Foundation for Infectious Diseases. As the CDC recognizes, the disease 

disproportionately affects college students who often live in close quarters at university 

dormitories. 

But while the Food and Drug Administration recently approved two meningitis B vaccines, many 

students do not yet get immunized against this strain of meningitis. Adding the vaccine to the 

standard schedule of immunization would increase the likelihood of students receiving it, 

improving university populations’ safety and health. 

College students embody our states’ bright futures, and they deserve to be protected against 

preventable death and disability. Thus, at the June meeting of your Advisory Committee on 

Immunization Practices, please opt to comprehensively recommend the meningitis B 

immunization. By doing so, you can help to shield college campuses from disease outbreaks and 

ensure that students across the nation do not unnecessarily face this deadly disease. 

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Sincerely, 

Alliance for Patient Access 

Health Policy Council members 

State Representative Jim Neely, D.O. 

Family Practice 

Cameron, Missouri 

 State Senator Tom Takubo, D.O. 

Pulmonology/CCM 

South Charleston, West Virginia 

State Senator Elizabeth Steiner Hayward, M.D.

Family Medicine 

Portland, Oregon 

 State Representative David Watkins, M.D. 

Family Medicine 

Henderson, Kentucky 

*The Alliance for Patient Access receives financial support from a broad range of associate 

members, donors, and sponsors including Pfizer, Inc. and GlaxoSmithKline plc, both 

manufacturers of meningitis B vaccines. 

Alliance for Patient Access 

2000 M Street NW, Suite 850 

Washington, DC 20036 

http://allianceforpatientaccess.org/health-policy-council/ 

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